A novel mutation of the USH2C (GPR98) gene in an Iranian family with Usher syndrome Type II

Usher syndrome (USH) is an autosomal recessive disorder illustrated with retinitis pigmentosa (RP) and sensorineural hearing loss with or without variable vestibular dysfunction. USH is genetically and clinically heterogeneous. At least fifteen loci and eleven genes identified in USH. Usher syndrome is divided into three subtype: type I (USH1); type II (USH2); and type III (USH3). USH2 is the most common form of Usher syndrome, responsible for moderate to severehearing deficits, retinitis pigmentosa started around or after puberty associated with normal vestibular responses. Threeloci associated with USH2 have been reported: USH2A (USH2A), USH2C (GPR98), and USH2D (WHRN). Defects inGPR98 are the cause of Usher syndrome type 2C (USH2C). Here, we report on a consanguineous Iranian family with two affected individuals for whom we identified a novel mutation in GPR98 (VLGRI) gene. After performing homozygosity mapping using microsatellite (STR) markers,we approached whole exome sequencing (WES) to detect the disease-causing mutation of homozygous regions. To confirm the identified homozygote variant in GPR98, sanger sequencing hasperformed in all family members. Consequently we sequenced 100 normal control to ensure detected variant would not be a polymorphism. We identified a new mutation in GPR98 segregating with USH2C in this family. The missense mutation c.10019T>G leading to p.Val3340Gly. This mutation is the second one, which has been reported for USH2C in Iranian population by our group. To the best of our knowledge, this is the first report of a genetically confirmed case of USH2C using WES in Iran

Keywords:

Usher 2C , GPR98 , whole exome sequencing , novel mutation , Iran