Spectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan.

TitleSpectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan.
Publication TypeJournal Article
Year of Publication2020
AuthorsRamzan, M, Bashir, R, Salman, M, Mujtaba, G, Sobreira, N, P Witmer, D, Naz, S
Corporate AuthorsBaylor-Hopkins Center for Mendelian Genomics
JournalSci Rep
Volume10
Issue1
Pagination11902
Date Published2020 Jul 17
ISSN2045-2322
Abstract

Hearing loss affects 380 million people worldwide due to environmental or genetic causes. Determining the cause of deafness in individuals without previous family history of hearing loss is challenging and has been relatively unexplored in Pakistan. We investigated the spectrum of genetic variants in hearing loss in a cohort of singleton affected individuals born to consanguineous parents. Twenty-one individuals with moderate to severe hearing loss were recruited. We performed whole-exome sequencing on DNA samples from the participants, which identified seventeen variants in ten known deafness genes and one novel candidate gene. All identified variants were homozygous except for two. Eleven of the variants were novel, including one multi-exonic homozygous deletion in OTOA. A missense variant in ESRRB was implicated for recessively inherited moderate to severe hearing loss. Two individuals were heterozygous for variants in MYO7A and CHD7, respectively, consistent with de novo variants or dominant inheritance with incomplete penetrance as the reason for their hearing loss. Our results indicate that similar to familial cases of deafness, variants in a large number of genes are responsible for moderate to severe hearing loss in sporadic individuals born to consanguineous couples.

DOI10.1038/s41598-020-68779-5
Alternate JournalSci Rep
PubMed ID32681043
PubMed Central IDPMC7368073
Grant ListU54 HG006542 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
NHGRI 1U54HG006542 / / Baylor Hopkins Center for Mendelian Genetics /
UM1HG006542 / / Baylor Hopkins Center for Mendelian Genetics /
3288 / / Higher Education Commission, Pakistan /