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A new locus for autosomal dominant high myopia maps to 4q22-q27 between D4S1578 and D4S1612.

PURPOSE
Myopia is the most common visual problem in the world. High myopia, the extreme form of myopia that can be complicated by retinal detachment and macular degeneration, affects 1%-2% of the general population. The genes responsible for nonsyndromic high myopia have not been identified although several chromosome loci have been suggested. Additional loci for the majority of high myopia, especially in Asian populations, await discovery. A large Chinese family with autosomal dominant high myopia was collected in order to map the genetic locus as an initial step towards identifying the genetic cause of high myopia in this family.


METHODS
A Chinese family with 12 individuals affected with high myopia was ascertained from a small village in central China. Phenotypic information and DNA samples were collected from 18 individuals, including 11 affected and 7 unaffected individuals. A genome-wide scan was performed using markers spaced at about 10 cM intervals for genotyping and two-point linkage analysis was carried out. Candidate genes were sequenced.


RESULTS
High myopia, ranging from -5.00 D to -20.00 D with typical fundus changes, is transmitted as an autosomal dominant trait in this family. High myopia in this family shows linkage to markers in a 20.4 cM region between D4S1578 and D4S1612, with maximum lod scores of 3.11 and 3.61 at theta=0 by D4S1564 and by the D4S2986-D4S1572-D4S1564-D4S406-D4S1580-D4S402 haplotype, respectively. Sequence analysis of the retinal pigment epithelium-derived rhodopsin homolog (RRH; OMIM 605224) gene inside the linked region did not identify any causative mutations.


CONCLUSIONS
A novel locus (MYP11) for autosomal dominant high myopia in a Chinese family maps to 4q22-q27 but is not associated with mutations in RRH.