New and Rare GJB2 Alleles in Patients with Nonsyndromic Sensorineural Hearing Impairment: A Genotype/Auditory Phenotype Correlation

摘要

Aim: The aim of the study is to report the new and rare GJB2 variants identified in individuals with nonsyndromic sensorineural hearing impairment (HI) in a retrospective study based on 498 patients referred to the Otolaryngology and Medical Genetics Units of the Modena University Hospital, Italy, with the purpose of building new genotype/auditory phenotype correlations for the GJB2 gene. Results: A total of eight variants identified in HI patients under study were considered rare for their frequency below 1% in the general population and in the HI databases. Of those, four (I20T, V95M, N206S, c.-22-2A>C) were in compound heterozygosity with known mutations resulting in a range of phenotypes from mild to profound, whereas four (W3R, C218Y, K221N, c.-22-6T>C) were found in simple heterozygosity (for those only in silico prediction of pathogenicity was possible due to the absence of a second GJB2 or GJB6 mutation). Conclusion: Based on patients' phenotype, reported frequency, and in silico prediction analysis, we suggest the prognostic value of eight rare and new GJB2 alleles, which may be of help to the clinician in counseling patients who carry such variants.