Whole-Exome Sequencing Targeting a Gene Panel for Sensorineural Hearing Loss: The First Portuguese Cohort Study

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 theGJB2 gene and for duplications/deletions in theGJB6 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 inMYO15A,TMIE,TBC1D24,SPMX,GJB3,PCDH15, andCDH23 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 ofMYO3A,TECTA,EDNRB,TBC1D24, andGJB3 genes to SNHL. For the significant number of undiagnosed patients, reanalysis ...
Source: Cytogenetic and Genome Research - Category: Genetics & Stem Cells Source Type: research