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UK CMOs, Academy and GMC issue joint statement to support doctors throughout the second COVID-19 wave
11 November 2020
The Chief Medical Officers of all four UK nations, NHS England and NHS Improvement, General Medical Council and Academy of Medical Royal Colleges have today issued a statement to recognise that the peak of pressure from coronavirus infections will again require temporary changes to practice, and not...
Protect children for a challenging winter ahead
14 July 2020
The UK must prepare now for a potential new wave of coronavirus infections this winter that could be more serious than the first, says a new report from the Academy of Medical Sciences. Responding to 'Preparing for a challenging winter', the RCPCH made the following statement on vaccinations and pro...
What has COVID-19 told us about the future of paediatrics?
26 June 2020
RCPCH today publishes its first report from Paediatrics 2040, a major project looking at how paediatrics will change over the next 20 years.
Update on our courses for 2020
18 June 2020
To ensure the safety of our delegates and faculty, we are regretfully cancelling all face-to-face courses and events until at least January 2021. We're busy developing more online professional development opportunities, and look forward to updating you with more details soon.
Widening differences in UK child mortality are not inevitable
5 March 2020
Every death of a child or young person is a unique tragedy. In coping with such events as healthcare professionals, we respond in personalised ways. A common question, though, is whether we did everything we could to prevent it. Did we examine thoroughly? Did we respond to results quickly? Did we li...
Choose Paediatrics careers campaign – the challenge is real... and it's here now
25 September 2019
Paediatricians work in incredibly challenging times. But, say Camilla, the College's VP for Education & Professional Development and Hannah, Chair of Trainees Committee, this specialty is rewarding like no other, and there's much more we can all do.
No time to carry out child health research? Complete our short survey
29 June 2019
We believe that child health research should be embedded as part of every paediatrician's training, and throughout their careers. From June 2019 to 10 January 2020, we invited paediatricians working as consultants, SAS doctors and/or CCT holders to complete 2019 Participation in Child Health Researc...
Membership benefit for spring - volunteering opportunities
2 April 2019
Developing new skills, meeting new people, networking with like-minded colleagues, carrying out a sense of purpose... The benefits often outweigh the time given, which may be why more than 1,100 of you volunteer for the College. Whether it's representing your region or specialty on a committee, work...
Little improvement on reducing avoidable child deaths, new data shows
22 February 2019
The Office for National Statistics (ONS) has today published 2017 data on avoidable deaths.
"UK is lagging behind" – RCPCH responds to Nuffield Trust report
20 February 2019
The Nuffield Trust and the Association for Young People's Health have today published the first ever international comparison of young people's health measures over time, comparing the UK to 18 other high-income countries. Professor Russell Viner, President of the RCPCH, responds.


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Opportunity Overview
Our client is western Canada's leading commercial security solution provider and is looking for a Controller to join their team. Reporting to the General Manager, the Controller will be responsible for oversight of all finance, accounting, and reporting activity.
Job Responsibilities
- Prepare monthly financial statements, ensuring that financial transactions are complete
- Manage company's daily financial operations
- Maintain an adequate system of accounting records
- Maintain intercompany balances, financial statements, general ledger, accounts payable, accounts receivable and month-end tasks and requirements
- Daily cash management including bank reconciliations
- Ensure accuracy of the company's reported financial results
- Prepare financial documents such as business reports and financial statements to understand the financial state of the business
- Supervise a team of 3 accounting professionals
- Responsible for time management system processes and billing function
Core Skill Requirements
- 5 to 10 years' of relevant experience
- A post-secondary education focused in accounting
- Professional accounting designation required (CPA, CMA, CGA, CA)
- Proficiency with Quickbooks, Excel and all Microsoft Suite programs
- Strong attention to detail and a high level of accuracy in all areas of work
- Strong written and oral communication skills, professional, business-like demeanor with the ability to translate complex financial complex to non-finance individuals
- Strong work ethic with the ability to multi-task
How to Apply
Please submit your resume and cover letter in confidence to Susan Black, CPHR at email@example.com. Only qualified applicants will be contacted.

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John Henry Brown
Indian wars and pioneers of Texas online
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John Henry Brown
Indian wars and pioneers of Texas
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resulted in the American colonies throwing off the
yoke of British tyranny, and the establishment of
the United States of America, a monument to the
patriotism, valor and wisdom of the people of that
day which has no parallel in all the annals of
the human race. His maternal grandfather, Judge
James L. Burke, took part in the battle of the
Horse Shoe and fought through the War of 1812.
His father, Thomas Harris, was born near
Milledgeville in Georgia, September 15th, 1812,
was a farmer by occupation and died August 26,
1894, aged 82 years, in Comanche County, Texas,
where he then resided.
His mother, Mrs. Lydia Harris, was born in
Jasper County, Ga., January 28, 1816. Her
father moved to Talbot County, Ga. , when she was
a girl, and there she grew to womanhood, married
in 1835 and remained until 1845, when she moved
to Scott County, Miss., with her husband, where
she died in May, 1861, leaving nine children.
Judge A. J. Harris was six years of age when his
parents removed to Mississippi. He resided there
until after the close of the war. He graduated
from the University of Mississippi in 1861, with high
honors, and on returning home raised a company
for service in thie Confederate army and was elected
Captain. It^was mustered into service as Company
I, Twenty-seventh Mississippi Regimentof Infantry,
and did duty at Pensacola and Mobile, and in Ten-
essee and Kentucky. He participated with his com-
mand in several skirmishes and minor engagements
and took part in the great battle of Murfreesboro,
in all of (^which he bore himself with the coolness
and gallantry that became an ofHeer of one of the
grandest armies that ever marched forth to battle
for the rights ;and liberties of a people. On account
of physical disabilities he resigned his commission
in 1863 ; but subsequently, upon restoration to
health, rejoined the army, attaching himself as an
independent volunteer to the Fourth Mississippi
Cavalry and remained with it through the fall
and winter of 1863-64. From the spring of 1864
until August of that year, he was not connected
with the army, but, in August, Gen. Clark, then Gov-
ernor of Mississippi, issued a proclamation calling
on all who could bear arms even for thirty days to
go to North Mississippi and join the army under
Gen. Forrest, to meet the invading Northern army
of Gen. A. J. Smith. Responding to this call. Judge
Harris joined Duff's Regiment and served about
three months. He joined the regiment the next
day after he reached Forrest and marched with it
to Hurricane creek, north of Oxford, and remained
there night and day for several days under a constant
downpour of rain. The Confederate troops were
then driven back south of Oxford and went into
camp on Yocony creek. The next day the E'eder-
als burned Oxford and retreated with the Southern
army hanging upon their flank. The Confederates
overtook their rear guard at Abbeville and had a
slight brush with them which ended the campaign.
Judge Harris came to Waco, Texas, January 1st,
1865, and taught one month in the Waco Univer-
sity. He then went to Salado and taught in the
college at that place from February, 1865, until
July, 1867, after which he removed to Belton and
entered upon the practice of law, but was persuaded
by the people to open a school, which he taught
for two years. In 1869 he returned to the practice
of law ; but, in 1870, a vacancy occurring in the
faculty of the school at Salado, the people of that
place called upon him to fill it, promising to secure
another teacher to take his place, which they failed
to do, and he remained there one year, much against
his will. This service marked the close of his
career as a school-teacher. Returning to Belton,
he entered vigorously upon the practice of his
profession, in which he has since continued.
He was elected County Superintendent of public
free schools in 1873, and filled the office until the
adoption of the constitution of 1875, which dis-
pensed with county superintendents. He was
elected without opposition and without being a can-
didate. In 1880 he was elected to the State Senate
and was elected for a second term in 1882, serving
with marked distinction in the sessions of the Seven-
teenth and Eighteenth Legislatures. In 1877 he
formed a copartnership with X. B, Saunders, under
• Enj! by Y/TBaU er. BklynNX
^ ""S^b/ U6 ^ Koe /eta Me'VN' f-
the firm name of Harris & Saunders. Judge
Saunders succeeded Judge Alexander in the firm,
Judge Alexander having been appointed to the Dis-
trict Judgeship to succeed Judge Saunders, who was
the incumbent. This firm has occupied a lead-
ing position at the bar of Central Texas for many
Judge Harris was married July 31st, 1866, to Miss
Olivia P. Sugg, daughter of William and Mary
Sugg, of Calhoun County, Miss. They have six
children living: Mary, wife of S. S. Walker, a
merchant of Belton ; Martha Elizabeth, wife of
Pike L. Phelps, a gentleman engaged in the insur-
ance business, at Belton ; Olivia Frances, wife of
John P. Hammersmith, a Belton merchant; Lucy
Bell and Annie Jackson, who live at home and are
now students at Baylor College, and Andrew Jack-
son Harris, Jr. One son, Thomas, died July 9th,
1886, of membranous croup, aged two years and
six months.
Judge Harris has been a member of the Baptist
Church since 1876 and is one of the trustees of
Baylor Female College, at Belton.
He has never sought ofllce and has never been a
voluntary candidate ; nevertheless, at the State
Democratic Convention, held in 1886, his name was
submitted by his friends for nomination for one of
the judgeships of the Supreme Court of Texas, and
they claim that he received a majority of the votes
cast by the members of the convention, but on
account of some irregularities in counting them,
another ballot was taken and Judge R. R. Gaines
elected as the party's nominee.
Judge Harris occupies a position at the bar of
Texas, which he has so long graced with his learn-
ing and talents, that should be a matter of pride to
him and is certainly a source of gratification to his
thousands of admirers and many friends who ap-
preciate the dignity and purity of his character,
the value of the public services he has rendered
and the luster that he has added to the profession
which he has so long adorned.
T. W. House, veteran, merchant and banker of
Houston, was one of the notable pioneers of early
civilization and commerce in Texas. Born in
Somersetshire, England, in the year 1813, he died
at San Antonio, Texas, January 17th, 1880. His
forefathers were from Holland, from whence they
emigrated to England in the early dawn of the
eighteenth century, and settled in Somersetshire.
Up to the time that the subject of this memoir was
nineteen years of age, he worked on his father's
farm, but his father was poor, and, being the
youngest of four children, the future was not
bright, so he decided to come to America. He was
seconded in this resolution by a friend who was
captain of a merchant vessel plying between Bristol
and New York and with whom he set sail for
America in the year 1832. He remained in New
York for several years, and afterwards went to New
Orleans, where he lived for a short time before com-
ing to Texas. It was while living at New Orleans
that his attention was first called to Texas and her
wonderful resources, and early in the year 1836 he
landed in Galveston, and at once went to Houston,
which was then being laid out. It was at this
place that be was destined to achieve the full meas-
ure of his ambition. Soon after his arrival at
Houston he volunteered his services in behalf of
his adopted country and served as a soldier under
Gen. Burleson in the last days of the war of
1835-6, against Mexico. In 1838 he returned to
Houston and there, with the few hundred dollars
at his command, erected a tent, purchased a supply
of goods and began his wonderful career as a mer-
chant. His fortunes grew with the growth of the
town, to whose upbuilding he contributed perhaps
more than any other man, until he achieved the
rank of a merchant prince.
In 1840, he married Mary Ehzabeth, only daugh-
ter of Charles Shearn, afterwards Chief Justice of
Harris County. At the beginning of the war be-
tween the States in 1861, he had reached such a
position in the financial world that his advice and
services were sought by those in command, of the
Confederate forces in Texas, and he co-operated
effectively with them in the work of obtaining
clothes and arms from abroad. He owned jointly
with the Confederate Government, the Harriet
Lane, the celebrated Federal steamer which was
captured by the Confederates upon the retaking
ol Galveston by Magruder the night of December
31, 1862, and the day following. Besides his
interest in the Harriet Lane he also owned a fleet
of vessels which he used as blockade-runners in
conveying cotton out from Galveston and bringing
return cargoes of clothing and arms. With vast
resources at command, with a credit at home and
abroad excelled by none, with an unimpeachable
integrity, T. W. House did more perhaps during
the war between the States, than any other man in
Texas to maintain her credit abroad and supply the
wants of his fellow-citizens. His services in the
directions indicated were invaluable. When the
war was over he became actively engaged inducing
capital to invest in Texas and was a promoter of
several of the longest railroads in the State.
Among others he induced Commodore Morgan to
make large investments in Texas, and subsequently
to purchase $500,000 of the State's bonds. It was
this purchase that marked the beginning of the
credit which has given Texas bonds rank in the
stock market second to no similar class of securities
in the world. Charitable, without ostentation,
magnetic in manner, democratic in his tastes and
associations, he died beloved by many and honored
by all who knew him.
Leaving his native isle a penniless young man he
made his way into a new country, devastated by a
war marked by the most sanguinary atrocities and
the greater extent of whose territory was an unre-
deemed wilderness. Animated by the spirit of
ancient Cresy and Agincourt, like a true Briton, he
was as ready to use a musket as to settle down to
the more peaceful business of laying for himself
the foundation of financial iudependence. A wise
philosopher has said and said truly that the young
men who left their homes in foreign lands from
1800 to 1860 to come to America and push into its
wildernesses constituted a bold and enterprising
class and as a rule were possessed of more than
usual natural abilities. They were not content
with the hard conditions to which fate had ap-
parently consigned them. The plodder, the timor-
ous and the laggard might stay discontentedly
amid such scenes, but, as for these choice spirits, in
very childhood their eyes looked wistfully out to
sea and thoughts arose in their minds of lands
beyond the far-away horizon-bar, and these thoughts
gave birth to resolves, carried in due time into exe-
cution, to try their fortunes under other skies where
courage, self-reliance and ability insured honor-
able and useful careers. Such men as these came
to America by hundreds, and many of them to
Texas, among the number the subject of this
memoir, T. W. House. In their veins flowed rich
and ruddy the blood of the old Norman conquerors.
Where armed foes were to be met, they overcame
them. Where the wilderness was to be subdued,
they subdued it. Where cities were to be built,
they built them. Where the genius of commerce
was to be evoked they evoked it with the magic of
their indomitable wills. They were state and
nation builders who occupy a unique position upon
the pages of the history of the country, whose
services to posterity have been incalculable, whose
rugged virtues are worthy of all admiration, and
remembrance of whom should be preserved to
remotest time. Should the nation ever be in dan-
ger of sinking into effeminacy, those to whom is
committed its rejuvenation can turn to these men
as models to be imitated, and rebuild and restore
the vigor of the State.
Long before his death the name of T. W. House
had become a household word in Texas. He was
one of the foremost citizens of the commonwealth —
one of the most useful men of his day and genera-
tion. In his career he demonstrated the truth of
the aphorism of the author of Lacon that " while
fortune may be blind, she is by no means invisible,
and he who will seek her determinedly will be sure
to find her."
He has passed from shadow- land to shadow-land —
from birth to death.
He played his part nobly and well. May others
seek to emulate his example.
Jacob C. Higgins was born in Caledonia County,
Vt., November 2, 1815. His parents were Samuel
and Betsey (Chamberlain) Higgins. His father
came from Ireland and his mother from England.
They first met aboard a ship bound for America,
married and located in Caledonia County, Vt.,
where his father died, when the subject of this
memoir was four years of age, Mrs. Higgins follow-
ing him two years later. About a year after the
death of his mother Jacob C. Higgins fell into the
hands of an old sea-captain, Capt. Armington, who
was a TIniversalist and objected to his going to Sun-
day school. Consequently it became a regular
practice with the lad to play on that day with a
crowd of companions. On one of these occasions
while engaged in some sport, he was accosted by
Mr. Erastus Fairbanks, superintendent of the local
Presbyterian Sunday school, who asked him his
name, the names of his parents and .his place of
residence. In the conversation that followed, the
mutual discovery was made that Mr. Fairbanks'
wife was a first cousin of the boy's mother, and
a few days thereafter he was transferred to the
home of Mr. and Mrs. Fairbanks, where he was
treated in every respect as one of their sons, grew
to manhood and was given every opportunity to
perfect himself in the trade of a machinist and mill-
wright. He was quick to learn and soon became
proficient, and in 1836 was sent by the firm to
superintend the building of a saw-mill upon the
banks of one of the rivers of Alabama. This he
completed, and then engaged in steamboat
engineering, which he pursued for three years,
In 1840 he determined to try his fortune in
Texas, and landed in Galveston, March 16th of that
year, with $2,500 in good Alabama and Louisiana
money, the proceeds of a year's labor. With this
he purchased a .stock of merchandise from C. C.
Ennis, of Galveston, and went to Austin, where he
sold the goods for Texas money, which he discov-
ered, when too late, was of little or no value. He
had also bought a number of bonds. Regarding
these as worthless he laid them aside. They became
valuable later on, however, as Texas by the treaty
of annexation, sold the Santa Fe territory to
the United States for $10,000,000 and with a
part of the money so procured, called in and paid
off all outstanding bonds issued by the late Re-
public at their face value with all accumulated in-
terest thereon. Mr. Higgins, by this means, came
into possession of a considerable sum of money, his
profits on his bond purchases amounting to about
three hundred per cent. In June, 1840, soon after
his arrival in Austin, he was present at the organ-
ization of the first Methodist church established in
that town, and in fact in that section. Dr. Haney
held religious services in the old capitol on the
occasion referred to. When he called for all Meth-
odists present to come up and shake hands with
him, one man and one woman responded ; and with
these he organized the church. During the re-
mainder of that year Mr. Higgins was variously
engaged, part of the time working with a corps of
surveyors, and part of the time participating in
expeditions against the Indians.
In June, 1841, he moved to Bastrop, and was
there employed, to run a mill situated on Copperas
creek, two miles distant from town. In 1842 he
purchased the mill and ten acres of ground from
his employers on credit, and for years thereafter
husbanded his resources and invested all the money
that he could command in negroes and lands,
purchasing ten thousand acres of land in the sur-
rounding country and thereby laying the founda-
tion of future wealth.
He is an indefatigable worker and a clear-headed
financier, and hence prospered in all his business
undertakings. From the time that he landed in
Galveston to the annexation of Texas to the United
States, he endured many hardships and privations,
but thereafter when he had realized upon his bonds
and secured sufficient capital to operate upon,
lived more easily. He resided alone at the mill,
did his own cooking and housekeeping, and often,
for ten days at a time, did not see a human being
during the year 1842. In the early days of his
residence at Bastrop the Indians came into the
town and stole stock and committed numerous
depredations. About 1843, Bishop Morris, of
Baltimore, visited the place to see his son, and
while there preached in an old storehouse. During
the services a band of Indians, who were out on a
raid, broke up the meeting and the congregation was
obliged to fly for safety to a fort that had been
provided for such emergencies. During Mr. Hig-
gins' residence on Copperas creek he was also
frequently troubled by Indians. From 1871 to
1885 he added merchandising to his other busi-
ness. During these years he also established a
private bank. He continued banking until 1892,
when be retired from active pursuits.
He was first married in Bastrop County, in 1843,
to Miss Sarah Gamble, daughter of,Col. William I.
Gamble, who came to Texas from Alabama with
his family in 1839. By this marriage he had two
children : William, now a prosperous farmer in
Bastrop County, and Erastus Fairbanks Higgins,
who died leaving one child, Claud C, who now re-
sides with his grandfather. Mrs. Higgins died in
1849. Mr. Higgins was married at Seguin, in 1852,
to Miss Mary Keener, daughter of a prominent col-
lege professor of Alabama, and first cousin of
United States District Judge John B. Rector of
Texas. Five children were born of this union,
three of whom grew to maturity : Samuel, who is a
well-to-do farmer in Bastrop County ; Blanche,
wife of Brook Duval, of Bastrop County, and
Horace, who died June 4, 1880. Horace graduated
at the University of the South at Sewanee, Tenn.,
and later in the Law Department in the University
of Virginia. After returning home he formed a
co-partnership with Hon. Joseph D. Sayers, but he
died three months later, and thus came to a close
what promised to be a brilliant career at the bar.
Mrs. Mary (Keener) Higgins [died in Bastrop
County, in 1861.
In 1867, Mr. Higgins marriedjhis present wife,
Mrs. Carolina Yellowley, a widow with two daugh-
ters. The elder, Bella, married Dr. G. M. Patten,
of Waco, in 1883, and died in 1888. The younger,
Charlton, became Mrs. Brieger, and now resides in
Bowie, Texas. Mr. and Mrs. Higgins have two
daughters: Lielah, wife of D. Pope Holland, of
Atlanta, Ga., and Fairbanks who is now at Bishop
Garrett's College, at Dallas.
Upon returning to Texas in 1857, from a visit to
the home of Mrs. Fairbanks, in Vermont, Mr. Hig-
gins found that^he had been elected to the House of
Representatives of the Texas Legislature. He
served one term as a member of that body. He
could have been re-elected but would not consent
to become a candidate for that or any other political
oflBce. During the war between the States he
served in the Confederate States militia for twenty-
two months. He is a member of the Masonic
fraternity and has taken all the chapter degrees of
that order. In religion he is an Episcopalian, and
is senior warden of the Episcopal church at Bastrop.
In politics he is a Democrat. Although he lost
greatly by the result of the war between the States,
owning eighty valuable slaves who were set free at
its close, he has practically in all instances been
successful in his investments, and is now one of the
wealthiest men in his section and the largest tax-
payer in Bastrop County.
Up to his eleventh j'ear, when Providence discov-
ered him to his noble benefactors, Mr. and Mrs.
Fairbanks, the prospect that apparently laid before
him was cheerless. Whatever boyish hopes that
were to arise in his breast it seemed were doomed
to wither one by one, through long years of toil and
saddening disappointments, and in the end be
drifted to their graves adown the blasts of Destiny's
chill December. There was work for him to do in
life, however, and it was to come to him and be done
by him if he proved worthy. He did prove worthy
of the labor assigned him when the opportunity
came, and he embraced it.
He was grateful, he was honest, he was ambitious,
he was industrious, he was enterprising, he was
daring, resolute and patient, and as a result, his
life has been an honored, useful and successful
one. Had he failed in any of these particulars
this would not have been. Such a life contains a
moral that the young will do well to ponder and
profit by.
From the days when the commerce of Phcenicia
extended itself to the verge of the then known world
merchants have been the pioneers who have carried
forward the illumining torch of civilization. With-
out their energy and determination to attain success
amid difficulties apparently insurmountable, there
would be but little progress in wresting from nature
the waste places of the earth for the benefit of man-
kind. In the days when railroads were thought to
be impracticable and the telegraph a superstition,
a brave and hardy set of men were traveling over
Texas from end to end, on horseback, or in wagons.
cornf:lius ennis.
the compass being their only guide, or, if haply pre-
ceded by some comrade, they followed his footsteps
by means of the notches ^he had cut in trees. The
roads were almost impassable in rainy weather —
and, as there were no bridges, many an anxious
hour was spent at the fords. In traveling, pistols,
bowie knives and a gun across the knees, were
necessary to afford protection against man and
beast. Their avocation was, indeed, a perilous one,
but when have the sons of commerce been deterred
by peril ? They have braved alike the terrors of the
Barcan desert and the icy North, nor have they
feared to go among any savage people or travel any
foot of earth. Prominent among the pioneer mer-
chants of Texas was the subject of this memoir,
Cornelius Ennis, born in 1813 in Essex County
(now Passaic County), New Jersey. Mr.' Ennis'
great-grandfather was Mr. William Ennis, who
came from the north of Ireland in the latter part of
the seventeenth century, and settled in Bergen
County, New Jersey, with his wife (nee Miss Han-
nah Brower). Mr. Ennis' mother was a Doremus,
of Knickerbocker stock, from one of the original
Holland families that settled in this country.
After receiving as liberal an education as that
State then afforded, he went to New York in 1834,
and obtained a position in a drug store, and three
years later began a trip down the Ohio and Mis-
sissippi rivers in search of a desirable location.
Traveling on the Mississippi he met a great num-
ber of people from Texas, going to Canada to
join the patriots around Toronto. All were en-
thusiastic concerning the agricultural and business
opportunities afforded by Texas. These recitals
together with stories of the gallantry and courage
of the victors in the War for Independence, fired
the imagination of the young merchant — and he
determined to make his home in the Republic. He
returned to New York in May, continued in busi-
ness there until January, 1839, and then purchased
a stock of drugs and medicines and embarked on
the schooner " Lion " (Capt. Fish commanding)
for Galveston.
He found Galveston very sparsely settled, with-
out a hotel or wharf, and proceeded to Houston,
then two years old and the capital of the Republic.
Here he immediately established himself in busi-
ness, purchasing a lot on Main street, where he
built a storehouse. In November of the same
year he formed a partnership with Mr. George W.
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Indian wars and pioneers of Texas
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Original Research ARTICLE
TRPM7 as a Candidate Gene for Vestibular Migraine
- 1Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
- 2Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, South Korea
Objectives: Vestibular migraine (VM) is a common vestibular disorder, and familial aggregation of VM with autosomal-dominant inheritance has been described, which supports a genetic background. This study aimed to describe the clinical phenotype of a family with VM, and identify a candidate gene for VM.
Methods: We recruited six individuals (four affected and two unaffected) from three consecutive generations of a Korean family with VM, and performed whole-exome sequencing to search for candidate genes.
Results: All affected individuals presented with recurrent vertigo, headache, and nausea/vomiting that fulfilled the diagnostic criteria of VM. Two individuals also experienced transient hemiparesis or dysarthria during the episodes. The symptoms were triggered by physical or emotional stress. Interictal examinations showed uni- or bi-directional horizontal gaze-evoked nystagmus in three of the individuals. They had no causative mutations in genes causing familial hemiplegic migraine or episodic ataxia. Through whole-exome sequencing from three affected individuals, we identified a nonsense mutation c.3526C>T in TRPM7 that encodes a cation channel selective to Ca2+ and Mg2+.
Conclusions: Alterations in intracellular Ca2+ and Mg2+ homeostasis by TRPM7 mutation may contribute to the development of the VM phenotype. Our result suggest that TRPM7 is a novel candidate gene for VM.
Vestibular migraine (VM) is one of the most common vestibular disorders, affecting around 1% of the general population (1). It is characterized by recurrent attacks of vestibular symptoms, a current or previous history of migraine, and the existence of one or more migraine features during the vestibular episodes. Recently, VM has been included as a diagnostic category in the latest International Classification of Headache Disorders (ICHD) criteria (2).
Most cases of VM are considered sporadic, but familial aggregation of VM with autosomal-dominant inheritance has been described in several families, supporting a genetic background for the condition (3, 4). Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) associated with a genetic predisposition for migraine with or without aura (5, 6). Familial hemiplegic migraine (FHM), which is a subtype of migraine with aura, is caused by mutations in CACNA1A, ATP1A2, and SCN1A (7). However, no candidate gene has been validated in VM, although several genetic loci such as chromosomes 5q35, 9q13-q22, 11q, and 22q12 are known (8–11). Furthermore, previous studies have not detected pathogenic mutations in FHM or episodic ataxia (EA) genes in VM patients (12, 13).
Transient receptor potential (TRP) channels are a family of cation channels expressed mostly on the cell (14, 15). They are divided into seven subfamilies including TRPC, TRPV, TRPM, TRPA, TRPN, TRPP, and TRPML, which mediate sensory transduction such as pain, touch, hearing, and thermal sensation. In addition, TRP channels enable individual cells to respond to changes in their local environment. These ion channels have a relatively non-selective permeability to cations including Ca2+ and Mg2+, and modulate ion entry driving forces. TRP channels have been linked to neurodegenerative disorders, kidney disease, and cancers by altering intracellular ion homeostasis (15–18). Interestingly, they have been repeatedly hypothesized to contribute to migraine via the activation of meningeal nociceptors or the release of calcitonin gene-related peptide (CGRP) (19–22).
The present study investigated the clinical phenotype of a Korean family with VM showing autosomal-dominant inheritance. Here we report one novel mutation in TRPM7 that may explain the VM phenotype in the family.
Materials and Methods
Six individuals from three consecutive generations of a Korean family with VM (four affected and two unaffected individuals) were recruited at the Dizziness Clinic of Pusan National University Yangsan Hospital (Figure 1). VM was diagnosed based on the criteria of the Bárány Society (1). All individuals underwent full neurological and neuro-otological examinations by the author (J-HC), and the four affected individuals received brain magnetic resonance imaging to exclude other possible causes of their symptoms.
Figure 1. Pedigree of the Korean family with vestibular migraine. Solid symbols (squares for males and circles for females) indicate clinically affected individuals (open symbols are unaffected individuals and slashed symbols are deceased individuals). The proband is indicated by an arrow.
All experiments followed the tenets of the Declaration of Helsinki, and informed consents were obtained from the participants after the nature and possible consequences of this study had been explained to them. This study was approved by the institutional review boards of Pusan National University Hospital.
Whole-Exome Sequencing and Data Analysis
To systematically search for candidate genes, we applied trio exome sequencing to blood samples from three of the affected individuals (II-5, II-8, and III-3). Genomic DNA was extracted from the blood samples, and whole-exome sequencing was conducted using the SureSelect Focused Exome Kit (Agilent, Technologies, Santa Clara, CA, USA). Qualified genomic DNA samples were randomly fragmented by Covaris, followed by adapter ligation, purification, hybridization, and PCR. Captured libraries were analyzed using a bioanalyzer (Agilent 2100, Agilent Technologies) to estimate the quality, and they were loaded onto a sequencing system (Illumina HiSeq 2500, Theragen Etex Bio Institute, Suwon, Korea). Raw image files were processed for base-calling using HCS software (version 1.4.8) with default parameters, and the sequences of each individual were generated as 100-bp paired-end reads. Sequence reads were aligned to the human reference genome sequence (GRCh37.3, hg19) using the Burrows-Wheeler Aligner (version 0.7.12). PCR duplicate reads were marked and removed using Picard tools (version 1.92). The Genome Analysis Toolkit (version 2.3-9) was used for indel realignment and base recalibration. Variation annotation and interpretation analysis were performed using SnpEff (version 4.2).
For candidate gene screening, we first filtered heterozygous single-nucleotide variants (SNVs) and insertions/deletions (indels) shared by all affected individuals (Figure 2). Then, variants causing non-synonymous amino acid substitutions, stop codons, indels in coding regions, and changes to splice-site sequences at exon-intron boundaries were included. Common variants with a minor allele frequency (MAF) of >0.001 in the dbSNP147, the 1,000 Genomes Project, the NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD) were excluded. Since the frequency of variants may differ between racial groups, we further filtered rare variants with a MAF of <0.001 in the Korean Reference Genome Database (KRGDB). Candidate variants were identified and prioritized by performing functional annotation using the following tools: (1) the pathogenic variants risk composite score (PAVAR score), which is a seven-point scoring system based on annotations using SIFT (Sort Intolerant From Tolerant), PolyPhen2 (Polymorphism Phenotyping version 2), Grantham's Matrix, GERP+ (Genomic Evolutionary Rate Profiling), MutationTaster, PhastCons and PhyloP, (2) Combined Annotation-Dependent Depletion (CADD), and (3) Functional Analysis Through Hidden Markov Models (FATHMM). Variants with PAVAR score ≥5, CADD score ≥20, and FATHMM score ≤ -1.5 were considered to be potentially pathogenic (23). Finally, candidate variants were interpreted according to the standards and guidelines recommended by the American College of Medical Genetics and Genomics (ACMG) (24). The gene expression patterns were analyzed using public databases such as the Genotype-Tissue Expression (GTEx), BioGPS, and Serial Analysis of Gene Expression (SAGE), and the gene function was assessed using the HuGE Navigator, the GeneCards Human gene database, the Online Mendelian Inheritance in Man database, and PubMed. The candidate variants were validated by Sanger DNA sequencing, and were screened in another individuals within the family and 100 normal controls.
Figure 2. Filtering steps applied to the whole-exome sequencing data. CADD, Combined Annotation-Dependent Depletion; FATHMM, Functional Analysis Through Hidden Markov Models; Indels, insertions/deletions; PAVAR, pathogenic variants risk composite score; SNVs, single-nucleotide variants.
Clinical Phenotype
The clinical characteristics of the family are summarized in Table 1. All affected individuals presented with rotatory vertigo, headache, and nausea/vomiting lasting for several hours to days. All had a history of migraine with or without visual aura, and showed one or more migraine features during the vestibular episodes. Two individuals (I-2 and II-8) experienced transient hemiparesis during the attacks, one (II-8) of whom also had dysarthria and facial dysesthesia on the same side as the hemiparesis. The symptoms were triggered by physical or emotional stress. Two individuals also had auditory symptoms such as tinnitus (II-5) and ear fullness (II-8), but air-conduction audiograms showed normal hearing functions (Supplementary Figure 1). One individual (II-8) had a past history of recurrent seizure during her childhood. Between the vestibular episodes, three individuals (I-2, II-5, and III-3) showed uni- or bi-directional horizontal gaze-evoked nystagmus. The other neurological and neuro-otological examinations were unremarkable. Three individuals who received treatments showed a good response to flunarizine (II-5 and II-8) or propranolol (III-3).
Genetic Analysis
An average of 5.49 billion bases were generated per individual, with an average sequencing depth of approximately 63 in the target region, achieving the high quality of the sequencing (Supplementary Table 1). An initial screening of genes causing FHM and EA revealed no causative mutation in CACNA1A, ATP1A2, SCN1A, KCNA1, CACNB4, or SLC1A3.
The number of SNVs and indels identified per individual ranged from 120,657 to 123,359. Among them, a total of 2,586 variants were shared by all three individuals, and 508 of them were heterozygous non-synonymous missense variants, stop codons, coding indels, and splice-site variants at exon-intron boundaries (Figure 2). Next, 36 rare variants were filtered after excluding common variants with a MAF of >0.001 in public databases including gnomAD and KRGDB (Supplementary Table 2), but only two candidate variants in CDC27 and TRPM7 were prioritized by the functional annotations (Table 2). Both genes were found to be widely expressed in the brain including the cerebellum in public databases such as GTEx, BioGPS, and SAGE (Supplementary Figure 2).
Table 2. Candidate variants identified using bioinformatics tools after applying filtering and prioritization processes.
The CDC27 variant was a missense mutation c.71C>G of exon 2, which results in the amino acid substitution of alanine by glycine at codon 24. This gene participates in regulation of the cell cycle by encoding the anaphase-promoting complex, and is known to be associated with breast and prostate cancers. However, this variant was classified as "uncertain significance" in ACMG guidelines based on only one moderate (PM2) and three supporting (PP1, PP3, PP4) pathogenic criterion. Furthermore, a literature review did not reveal any evidence for a relationship between the CDC27 and our family's phenotypes including migraine, vertigo, vestibular or ataxic disorders. Thus, this variant was excluded as a candidate gene for VM.
The TRPM7 variant was a nonsense mutation c.3526C>T of exon 25 that cause a premature stop codon and loss-of-function in the protein. This variant was also present in another affected individual (I-2), while it was absent in the unaffected individuals (II-1 and II-10), 100 normal controls, gnomAD and KRGDB (Figures 3A,B). By applying ACMG guidelines, the variant was considered "pathogenic" based on one very strong (PVC1), one strong (PS3), one moderate (PM2), and three supporting (PP1, PP3, PP4) pathogenic criterion. The TRPM7 channel belongs to the melastatin subfamily of TRP channels, and it plays a crucial role in maintaining intracellular Ca2+ and Mg2+ homeostasis (Figure 3C). This has led to proposals that genetic variations in TRPM7 influence the susceptibility to neurodegenerative diseases (15, 16). In addition, SNVs within some TRP genes have been linked to migraine susceptibility (5, 25–27). Therefore, the TRPM7 variant may be a causal variant for explaining the phenotypes in the present family.
Figure 3. (A) Chromatograms of the affected individuals showing a heterozygous nonsense mutation (c.3526C>T) in exon 25 of TRPM7, which would result in a premature stop codon (p.Gln1176*). (B) Conservation of the mutated residue (Gln, Q) of a "connecting helix" (CH) in the C-terminus, highlighted in gray. (C) Schematic representation of the TRPM7 channel and localization of the mutation. The TRPM7 channel comprises a tetrameric complex with each subunit containing six-transmembrane segments (S1–S6) and a pore-forming loop between S5 and S6. Its cytoplasmic N-terminus has four regions of TRPM subfamily homology domain (MHD), whereas the C-terminus contains a TRP box of highly conserved residues, a coiled-coil (CC) domain, and an atypical serine/threonine protein kinase domain. The mutation (p.Gln1176*) is located in a CH that links the transmembrane segment and the CC domain in the C-terminus (arrow).
This study identified a nonsense mutation in TRPM7 in a Korean family with VM. This variant may cause a premature stop codon and loss-of-function in the protein, thus contributing to the development the VM phenotype by altering the homeostasis of intracellular ions.
Several hypotheses have been proposed for explaining the pathophysiology of VM, which remains unclear. The genetic susceptibility of migraine suggests ionic channelopathy involved in glutamate homeostasis as the underlying pathophysiology of VM (28, 29). Indeed, there is accumulating evidence that Ca2+ channels could be involved in migraine and VM pathophysiology. Mutations in CACNA1A, which encodes Cav2.1, the α1A subunit of the P/Q-type voltage-gated Ca2+ channel, cause three neurological channelopathies: FHM type 1, EA type 2 (EA2), and spinocerebellar ataxia type 6 (30). Patients with FHM or EA2 often experience paroxysmal vertigo, and more than half of EA2 patients have migraine that meets the ICHD criteria. Some members of the present family also presented with hemiplegia and dysarthria during their episodes. Nevertheless, previous studies failed to detect mutations in patients with VM in the genes causing FHM or EA, such as CACNA1A, ATP1A2, SCN1A, and CACNB4 (12, 13), which is consistent with the present study.
TRPM7 reported here encodes the cation selective ion channel that is highly permeable to Ca2+, Mg2+, and metal ions such as Zn2+ (16). This channel comprises a tetrameric complex, with each subunit containing six-transmembrane segments (S1–S6) and a pore-forming loop between S5 and S6 [Figure 3C; (31)]. Its C-terminus contains a TRP box of highly conserved residues, a coiled-coil (CC) domain, and an atypical serine/threonine protein kinase domain (32). The TRPM7 mutation identified in the present study is located in a long "connecting helix" that links the transmembrane segment and the CC domain in the C-terminus, thus predicting truncation of the C-terminus including the CC and kinase domains (32). These domains play an important role in the tetrameric assembly of the channel or in regulating channel function by Mg2+ nucleotides (31–34). Therefore, the mutation identified in the present study seems to affect TRPM7 channel activity via structural instability or functional impairment. This hypothesis is supported by a previous animal study which generated knockout mice with the deletion of TRPM7 kinase domain (35). These mice carried truncated mutation quite similar to the mutation described in this study. Although homozygous knockout mice caused embryonic lethality, heterozygous mice were viable, but showed abnormality in the regulation of Mg2+ homeostasis and alterations in TRPM7 channel properties. These mice exhibited abnormal behaviors such as clasping, tremor, seizure, and violent sudden leaps as a reaction to the light and noise, similar to photophobia and phonophobia seen in VM. Furthermore, one of the affected individuals in this family had a history of recurrent seizure.
Ca2+ and Mg2+ play important roles in regulating various neuronal functions. In particular, they exert opposite effects in the signaling of the excitatory neurotransmitter glutamate: glutamate release is triggered by an influx of Ca2+, whereas Mg2+ inhibits glutamate release by antagonizing Ca2+ (36). Thus, a tight balance between Ca2+ and Mg2+ is needed in order to maintain the proper excitability of neurons. Since TRPM7 channels that are abundantly expressed in neuronal cells are highly selective to Ca2+ and Mg2+ (37, 38), mutation in TRPM7 may cause alterations in Ca2+ and Mg2+ homeostasis and neuronal excitability. Migrainous headache is the consequence of cortical spreading depression evoked by glutamate release and N-methyl-D-aspartate (NMDA) receptor activation in the brain. These processes have been linked to low Mg2+ concentrations, which contribute to the hyperexcitability of the NMDA receptor (36). A beneficial effect of Mg2+ supplementation has also been reported in migraine patients (39). In addition, low Mg2+ concentrations increase the amount of substance P released, which is a neuroinflammatory mediator (40). Since the TRPM7 channel is an important Mg2+ transporter, it may contribute to VM attacks by affecting intracellular Ca2+ and Mg2+ homeostasis.
Recently, several TRP channels have been linked to migraine pathophysiology, including TRPV1, TRPV4, TRPM8, and TRPA1 (19). These channels are expressed on trigeminal sensory neurons that innervate the meninges (20, 41). The activation of TRP channels promotes the excitation of nociceptive afferent fibers and potentially leads to pain and allodynia (19, 20). In addition, it can elicit the release of CGRP, causing vasodilation and neurogenic inflammation (19, 42, 43). Several SNPs in TRPV1, TRPV3, and TRPM8 were found to be associated with migraine susceptibility in meta-analyses of observational studies and GWAS (5, 25–27). Based on these findings, TRP channels have been proposed as a therapeutic target in migraine (19, 21, 22, 44). More studies are needed to better explore the potential role for these channels including TRPM7 in migraine pathophysiology.
This study was subjective to some potential limitations. We did not perform functional study determining pathogenicity of the candidate variants. Despite the rarity and putative pathogenicity in functional annotations, establishing the pathogenicity of the variants may be difficult without a functional assay. However, previous functional studies demonstrated that the deletion of TRPM7 kinase domain reduced channel activity and increased its sensitivity to Mg2+ inhibition (33–35). Another limitation is difficulty in detecting copy number variations (CNVs) through whole-exome sequencing. CNV analysis can aid the detection of large deletions or duplications of causative genes, but whole-genome sequencing may be more suitable than whole-exome sequencing for CNV analysis. Finally, we used the hg19 as the reference genome for the reads mapping instead of hg38.
In summary, we have presented the clinical characteristics of a Korean family with VM. Whole-exome sequencing identified a potential disease-causing variant in TRPM7, which may cause alterations in intracellular Ca2+ and Mg2+ homeostasis and neuronal excitability. Our results highlight TRPM7 as a novel candidate gene for VM.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics Statement
The studies involving human participants were reviewed and approved by Pusan National University Yangsan Hospital. The patients/participants provided their written informed consent to participate in this study.
Author Contributions
EO conducted the experiments and interpretation of the data, and wrote the manuscript. J-HS, JC, S-YC, and K-DC contributed to the interpretation and analysis of data. J-HC conducted the design and conceptualization of the study, interpretaion of the data, and revised the manuscript. All authors contributed to the article and approved the submitted version.
This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2018R1D1A1A09081786).
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Supplementary Material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2020.595042/full#supplementary-material
1. Lempert T, Olesen J, Furman J, Waterston J, Seemungal B, Carey J, et al. Vestibular migraine: diagnostic criteria. J Vestib Res. (2012) 22:167–72. doi: 10.3233/VES-2012-0453
2. Headache Classification Committee of the International Headache Society (IHS). The International classification of headache disorders, 3rd Edition. Cephalalgia. (2018) 38:1–211. doi: 10.1177/0333102417738202
3. Frejo L, Giegling I, Teggi R, Lopez-Escamez JA, Rujescu D. Genetics of vestibular disorders: pathophysiological insights. J Neurol. (2018) 263(Suppl. 1):S45–53. doi: 10.1007/s00415-015-7988-9
4. Roman-Naranjo P, Gallego-Martinez A, Lopez Escamez JA. Genetics of vestibular syndromes. Curr Opin Neurol. (2018) 31:105–10. doi: 10.1097/WCO.0000000000000519
5. Chasman DI, Schürks M, Anttila V, Vries BD, Schminke U, Launer LJ, et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet. (2011) 43:695–8. doi: 10.1038/ng.856
6. de Boer I, van den Maagdenberg AMJM, Terwindt GM. Advance in genetics of migraine. Curr Opin Neurol. (2019) 32:413–21. doi: 10.1097/WCO.0000000000000687
7. Jen JC. Familial Hemiplegic Migraine. GeneReviews. Seattle, WA: University of Washington (2001).
8. Bahmad F Jr, DePalma SR, Merchant SN, Bezerra RL, Oliveira CA, Seidman CE, et al. Locus for familial migrainous vertigo disease maps to chromosome 5q35. Ann Otol Rhinol Laryngol. (2009) 118:670–6. doi: 10.1177/000348940911800912
9. Peddareddygari LR, Kramer PD, Hanna PA, Levenstien MA, Grewal RP. Genetic analysis of a large family with migraine, vertigo, and motion sickness. Can J Neurol Sci. (2019) 46:512–7. doi: 10.1017/cjn.2019.64
10. Lee H, Jen JC, Cha YH, Nelson SF, Baloh RW. Phenotypic and genetic analysis of a large family with migraine-associated vertigo. Headache. (2008) 48:1460–7. doi: 10.1111/j.1526-4610.2007.01002.x
11. Lee H, Jen JC, Wang H, Chen Z, Mamsa H, Sabatti C, et al. A genome-wide linkage scan of familial benign recurrent vertigo: linkage to 22q12 with evidence of heterogeneity. Hum Mol Genet. (2006) 15:251–8. doi: 10.1093/hmg/ddi441
12. Kim JS, Yue Q, Jen JC, Nelson SF, Baloh RW. Familial migraine with vertigo: no mutations found in CACNA1A. Am J Med Genet. (1998) 79:148–51. doi: 10.1002/(SICI)1096-8628(19980901)79:2<148::AID-AJMG11>3.0.CO;2-J
13. von Brevern M, Ta N, Shankar A, Wiste A, Siegel Anne, Radtke A, et al. Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4. Headache. (2006) 46:1136–41. doi: 10.1111/j.1526-4610.2006.00504.x
14. Clapham DE. TRP channels as cellular sensors. Nature. (2003) 426:517–24. doi: 10.1038/nature02196
15. Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem. (2007) 76:387–417. doi: 10.1146/annurev.biochem.75.103004.142819
16. Sun Y, Sukumaran P, Schaar A, Singh BB. TRPM7 and its role in neurodegenerative diseases. Channels. (2015) 9:253–61. doi: 10.1080/19336950.2015.1075675
17. Markó L, Mannaa M, Haschler TN, Krämer S, Gollasch M. Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2. Acta Physiol. (2017) 219:589–612. doi: 10.1111/apha.12828
18. Tajada S, Villalobos C. Calcium permeable channels in cancer hallmarks. Front Pharmacol. (2020) 11:968. doi: 10.3389/fphar.2020.00968
19. Benemei S, Dussor G. TRP channels and migraine: recent developments and new therapeutic opportunities. Pharmaceuticals. (2019) 12:54. doi: 10.3390/ph12020054
20. Huang D, Li S, Dhaka A, Story GM, Cao YQ. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura. Mol Pain. (2012) 8:66. doi: 10.1186/1744-8069-8-66
21. Dussor G, Yan J, Xie JY, Ossipov MH, Dodick DW, Porreca F. Targeting TRP channels for novel migraine therapeutics. ACS Chem Neurosci. (2014) 5:1085–1096. doi: 10.1021/cn500083e
22. Benemei S, Fusi C, Trevisan G, Geppetti P. The TRPA1 channel in migraine mechanism and treatment. Br J Pharmacol. (2014) 171:2552–67. doi: 10.1111/bph.12512
23. Requena T, Gallego-Martinez A, Lopez-Escamez JA. A pipeline combining multiple strategies for prioritizing heterozygous variants for the identification of candidate genes in exome datasets. Hum Genomics. (2017) 11:11. doi: 10.1186/s40246-017-0107-5
24. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular Pathology. Genet Med. (2015) 17:405–24. doi: 10.1038/gim.2015.30
25. Carreño O, Corominas R, Fernández-Morales J, Camina M, Sobrido MJ, Fernandez JM, et al. SNP variants within the vanilloid TRPV1 and TRPV3 receptor genes are associated with migraine in the Spanish population. Am J Med Genet B Neuropsychiatr Genet. (2012) 159B:94–103. doi: 10.1002/ajmg.b.32007
26. Key FM, Abdul-Aziz MA, Mundry R, Peter BM, Sekar A, D'Amato M, et al. Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. PLoS Genet. (2018) 14:e1007298. doi: 10.1371/journal.pgen.1007298
27. Chen SP, Fuh JL, Chung MY, Lin YC, Liao YC, Wang YF, et al. Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan. Cephalalgia. (2018) 38:466–475. doi: 10.1177/0333102417695105
28. Albury CL, Stuart S, Haupt LM, Griffiths LR. Ion channelopathies and migraine pathogenesis. Mol Genet Genomics. (2017) 292:729–39. doi: 10.1007/s00438-017-1317-1
29. Murofushi T, Tsubota M, Kitao K, Yoshimura E. Simultaneous presentation of definite vestibular migraine and definite Ménière's disease: overlapping syndrome of two diseases. Front Neurol. (2018) 9:749. doi: 10.3389/fneur.2018.00749
30. Choi KD, Choi JH. Episodic ataxias: clinical and genetic features. J Mov Disord. (2016) 9:129–135. doi: 10.14802/jmd.16028
31. Park HS, Hong C, Kim BJ, So I. The pathophysiologic roles of TRPM7 channel. Korean J Physiol Pharmacol. (2014) 18:15–23. doi: 10.4196/kjpp.2014.18.1.15
32. Duan J, Li Z, Li J, Hulse RE, Santa-Cruz A, Valinsky WC, et al. Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc Natl Acad Sci USA. (2018) 115:E8201–10. doi: 10.1073/pnas.1810719115
33. Runnels LW, Yue L, Clapham DE. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science. (2001) 291:1043–7. doi: 10.1126/science.1058519
34. Demeuse P, Penner R, Fleig A. TRPM7 channel is regulated by magnesium nucleotides via its kinase domain. J Gen Physiol. (2006) 127:421–34. doi: 10.1085/jgp.200509410
35. Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, Yamaguchi TP, et al. TRPM7 is essential for Mg(2+) homeostasis in mammals. Nat Commun. (2010) 1:109. doi: 10.1038/ncomms1108
36. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. (2015) 95:1–46. doi: 10.1152/physrev.00012.2014
37. Kunert-Keil C, Bisping F, Krüger J, Brinkmeier H. Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics. (2006) 7:159. doi: 10.1186/1471-2164-7-159
38. Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S. Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res. (2006) 26:159–78. doi: 10.1080/10799890600637506
39. Dolati S, Rikhtegar R, Mehdizadeh A, Yousefi M. The role of magnesium in pathophysiology and migraine treatment. Biol Trace Elem Res. (2020) 196:375–83. doi: 10.1007/s12011-019-01931-z
40. Weglicki WB, Phillips TM. Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. Am J Physiol. (1992) 263(3 Pt 2):R734–7. doi: 10.1152/ajpregu.1992.263.3.R734
41. Burgos-Vega C, Moy J, Dussor G. Meningeal afferent signaling and the pathophysiology of migraine. Prog Mol Biol Transl Sci. (2015) 131:537–64. doi: 10.1016/bs.pmbts.2015.01.001
42. Veldhuis NA, Poole DP, Grace M, McIntyre P, Bunnett NW. The G protein-coupled receptor-transient receptor potential channel axis: molecular insights for targeting disorders of sensation and inflammation. Pharmacol Rev. (2015) 67:36–73. doi: 10.1124/pr.114.009555
43. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. (2014) 94:1099–142. doi: 10.1152/physrev.00034.2013
44. Artero-Morales M, González-Rodríguez S, Ferrer-Montiel A. TRP channels as potential targets for sex-related differences in migraine pain. Front Mol Biosci. (2018) 5:73. doi: 10.3389/fmolb.2018.00073
Keywords: vestibular migraine, genetics, whole-exome sequencing, TRPM7 channel, ion homeostasis
Citation: Oh EH, Shin J-H, Cho JW, Choi S-Y, Choi K-D and Choi J-H (2020) TRPM7 as a Candidate Gene for Vestibular Migraine. Front. Neurol. 11:595042. doi: 10.3389/fneur.2020.595042
Received: 14 August 2020; Accepted: 29 September 2020;
Published: 23 October 2020.
Edited by:Jose Antonio Lopez-Escamez, Andalusian Autonomous Government of Genomics and Oncological Research (GENYO), Spain
Reviewed by:Alvaro Gallego-Martinez, Granada Biosanitary Research Institute (ibs.Granada), Spain
Matias Morin, Center for Biomedical Research in Rare Diseases Network (CIBERER), Spain
Copyright © 2020 Oh, Shin, Cho, Choi, Choi and Choi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jae-Hwan Choi, email@example.com


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Staying productive
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Platform agnostic
An iPhone 6S is Bhargava's primary handset. "I have been thinking of upgrading but haven't found enough reasons to," he says, justifying his attachment to the device.
He also carries a OnePlus 6T. "I don't indulge in debates around Android vs iPhone as both are good with what they do. The iOS platform offers pure ease of use, while Android gives you access to quality apps for free," Bhargava says.
But the tech boss knows when to stop before his phones turn to be a distraction. "I refrain from using my phones when I am in a meeting or having a conversation with someone," he says.
Fiction turned reality
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App-solutely useful
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