Genetic causes of moderate to severe hearing loss point to modifiers.

Autor: Naz S; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Imtiaz A; School of Biological Sciences, University of the Punjab, Lahore, Pakistan.; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Mujtaba G; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Maqsood A; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Bashir R; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Bukhari I; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Khan MR; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Ramzan M; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Fatima A; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Rehman AU; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Iqbal M; School of Biological Sciences, University of the Punjab, Lahore, Pakistan., Chaudhry T; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Lund M; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Brewer CC; Audiology Unit, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Morell RJ; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892.; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892., Friedman TB; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA 20892.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2017 Apr; Vol. 91 (4), pp. 589-598. Date of Electronic Publication: 2016 Oct 06.
DOI: 10.1111/cge.12856
Abstrakt: The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness. We recruited 92 consanguineous families segregating stable or progressive, recessively inherited moderate or severe hearing loss. We utilized homozygosity mapping, Sanger sequencing, targeted capture of known deafness genes with massively parallel sequencing and whole exome sequencing to identify the molecular basis of hearing loss in these families. Variants of the known deafness genes were found in 69% of the participating families with the SLC26A4, GJB2, MYO15A, TMC1, TMPRSS3, OTOF, MYO7A and CLDN14 genes together accounting for hearing loss in 54% of the families. We identified 20 reported and 21 novel variants in 21 known deafness genes; 16 of the 20 reported variants, previously associated with stable, profound deafness were associated with moderate to severe or progressive hearing loss in our families. These data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity.
(© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: