摘要 : Next-generation sequencing (NGS) technologies revolutionized the molecular diagnosis of sensorineural hearing loss (SNHL) and are now a standard of care. In this study, 71 Portuguese probands with hereditary SNHL were assessed by ... 展开 Next-generation sequencing (NGS) technologies revolutionized the molecular diagnosis of sensorineural hearing loss (SNHL) and are now a standard of care. In this study, 71 Portuguese probands with hereditary SNHL were assessed by whole-exome sequencing (WES) targeting a panel of 158 genes related to SNHL, aiming to evaluate the diagnostic yield of this methodological approach and to report the spectrum of variants. Patients with either nonsyndromic or syndromic SNHL were included. Also, patients were previously screened for variants in the GJB2 gene and for duplications/deletions in the GJB6 gene. Causative variants in 11 different genes were identified in 15 (21.1%) out of 71 probands, 5 of which had associated syndromes. In 6 other patients (8.5%), presumptive causative variants were identified in MYO15A, TMIE, TBC1D24, SPMX, GJB3, PCDH15, and CDH23 genes, uncovering a potential case of digenic Usher syndrome. The study was inconclusive in 20 probands (28.2%), in 19 due to lack of segregation analysis and in one due to uncertain phenotype-genotype matching. In the remaining 30 patients (42.3%) no potentially causative variants were identified. The diagnostic yield did not significantly vary according to the age of hearing-impairment onset. As the first study on the application of NGS technologies in SNHL based on a Portuguese cohort, our results may contribute to characterize the spectrum of variants related to SNHL in the Portuguese population. Additionally, the present study provides new insights into the contribution of MYO3A, TECTA, EDNRB, TBC1D24, and GJB3 genes to SNHL. For the significant number of undiagnosed patients, reanalysis of WES data – either for a broader gene panel or in a non-targeted approach – may be considered. 收起