ABSTRACT
Usher syndrome [USH] is a clinically and genetically heterogeneous disease. The three recognized clinical phenotypes, USH1, USH2 and USH3, are caused by mutations in nine different genes. USH2C is characterized by moderate-to-severe hearing loss, retinitis pigmentosa and normal vestibular function. Earlier reports describe mutations in VLGR1 in five families segregating this phenotype. We ascertained an Iranian family, in which nine family members were found to have hearing loss. Five patients were diagnosed to have Usher syndrome, while two individuals have nonsyndromic hearing loss. Consistent with these clinical findings, the five subjects with USH carried a haplotype linked to the USH2C locus, while the two subjects with nonsyndromic hearing loss did not, indicating that their hearing loss is due to another genetic cause. We identified a new mutation in VLGR1 segregating with the USH2C in this family. The mutation is a large deletion g.371657-507673del containing exons 84 and 85 and is presumed to lead to a frameshift. The deletion probably arose by replication slippage caused by the presence of a short 7-bp repeat at the deletion breakpoints. No genotype-phenotype correlation could be found for USH2C. In the family described, the first male subjects with USH2C and a VLGR1 mutation have been identified