Non-syndromic hearing loss (NSHL) is characterized by a vast genetic heterogeneity; some syndromic forms as Usher syndrome (USH) have onset as isolated deafness and then evolve later in life. We developed an NGS targeted gene-panel containing 59 genes and a customized bioinformatic pipeline for the analysis of DNA samples from clinically highly selected subjects with sensorineural hearing loss, previously resulted negative for GJB2 mutations/GJB6 deletions. Among the 217 tested subjects, 24 (11.1%) were found to carry mutations in genes involved both in NSHL and USH. For 6 out of 24 patients a diagnosis of USH was performed. Eleven subjects out of 24 had hearing loss without vestibular or ocular dysfunction and, due to their young age, it was not possible to establish whether their phenotype could be NSHL or USH. Seven subjects were diagnosed with NSHL, due to their age and phenotype. A total of 41 likely pathogenic/pathogenic mutations were identified, among which 17 novel ones. We report a high frequency of mutations in genes involved both in NSHL and in USH in a cohort of individuals tested for seemingly isolated deafness. Our data also highlight a wider than expected phenotypic variability in the USH phenotype.

非综合征性听力损失（NSHL）的特征是遗传异质性很强。某些症状如Usher综合征（USH）会先因独立性耳聋发作，然后在生命后期发展。我们开发了包含59个基因的NGS靶向基因面板和定制的生物信息流水线，用于分析临床上高度选择的具有感音神经性听力损失的受试者的DNA样品，以前对GJB2突变/ GJB6呈阴性删除。在217名接受测试的受试者中，发现24名（11.1％）携带与NSHL和USH相关的基因突变。24名患者中有6名进行了USH诊断。24名患者中有11名患有听力丧失而没有前庭或眼功能障碍，并且由于年龄较小，无法确定其表型是NSHL还是USH。由于年龄和表型，七名受试者被诊断出患有NSHL。总共鉴定出41种可能的致病/致病突变，其中17种是新颖的。我们报道了在一组似乎看似孤立的耳聋的个体中，NSHL和USH中涉及的基因突变的频率很高。我们的数据还表明，USH表型的表型变异性超出预期。