Usher Syndrome (US) is an autosomal recessive condition characterised by a combination of congenital hearing impairment and retinitis pigmentosa. To date, ten genes have been associated with US, representing up to 90% of cases. Three types of US are known and differ by onset of the symptoms, severity and progressiveness of deafness and additional vestibular dysfunction. Patients with type II US have congenital bilateral sensor neural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies, intact vestibular responses, and bilateral retinitis pigmentosa.
40 unrelated Usher II type families (60 patients) from Volga-Ural Region of Russia were studied using genotyping micro array (Usher, Asper-Biotech) for screening 614 mutations in genes CDH23, MYO7A, PCDH15, USH1C, USH1G, USH2A, GPR98, CLRN1, DFNB31 and automatic sequencing of Usher’s genes. Diagnosis was based on pedigree data, ophthalmologic, audio logical and vestibular examination.
We revealed homozygous and heterozygous genotypes for the c.11864G >A (p. Trp3955X) mutation (USH2A) in six unrelated families among Russian, Tatar and Chuvash patients with Usher II syndrome. We found four pathogenic mutations in coding region of 8 patients (p. Glu4458fs, p. Trp3955X, p. Glu4078fs, and p. Gly1392X), confirming their clinical diagnosis. The most frequent USH2A gene mutation was c.11864G >A (9/80 alleles; 11,25%). Mutation c.11864G >A in heterozygous state was also found in one Russian subject out of 1066 examined individuals from 16 various populations of Eurasia: Bashkirs, Tatars, Chuvashes, Udmurts, Komi-Permyaks, and Mordvins, Russians, Belarusians, Ukrainians, Veps, and Karelians, Abkhazians, Kazakhs, Uzbeks, Yakuts, Altaians. Study was supported by grants (No12–04–00342_a, No12–04–98520_r_vostok_a, 14–04–97002_r_povolgie_a, 14–04–97007_r_povolgie_a,14–04–01741_A).