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Novel mutation in TSPAN12 associated with familial exudative vitreoretinopathy in a Chinese pedigree

ABSTRACT Background Familial exudative vitreoretinopathy (FEVR) is a rare retinal disorder characterised by incomplete retinal vascular development. Symptoms vary widely from none to blindness even within the same family. Multiple genes related to the Wnt pathway have been found to be associated with FEVR. Recent studies identified tetraspanin 12 (TSPAN12) as a cause of the autosomal dominant inheritance form of FEVR. Here, we describe a novel TSPAN12 mutation in a Chinese family with FEVR. Methods Targeted next-generation sequencing was performed on the proband to define the TSPAN12 mutation. Sanger sequencing was used to confirm the mutation in five family members (I-1, II-2, II-3, II-4, and III-3) in a three-generation FEVR pedigree. Ophthalmologic examinations and diagnostic imaging related to FEVR were performed. Results The proband (II-3) was a 32-year-old man with early-stage peripheral retinal vascular anomalies, but no visual acuity problems. DNA sequencing identified a heterozygous missense mutation (c.241 G > A: p.Gly81Arg) in TSPAN12 in the proband. The mutation was in a highly conserved region and was predicted to affect the normal protein structure. The patient’s father and daughter were also diagnosed with FEVR and carried the same mutation, with varying degrees of manifestations. Other family members had good vision and normal eye examinations with negative genetic testing. Conclusions We identified a novel missense mutation in TSPAN12 associated with autosomal dominant FEVR. These results will facilitate the diagnosis, prognosis, and genetic counselling for this disease. Further studies are needed to identify the mechanisms underlying clinical variations among individuals in the family.