Exome sequencing of families from Ghana reveals known and candidate hearing impairment genes

Author:

Wonkam AmbroiseORCID,Adadey Samuel MawuliORCID,Schrauwen Isabelle,Aboagye Elvis Twumasi,Wonkam-Tingang Edmond,Esoh KevinORCID,Popel Kalinka,Manyisa Noluthando,Jonas Mario,deKock Carmen,Nembaware Victoria,Cornejo Sanchez Diana M.,Bharadwaj Thashi,Nasir AbdulORCID,Everard Jenna L.ORCID,Kadlubowska Magda K.,Nouel-Saied Liz M.,Acharya Anushree,Quaye OsbourneORCID,Amedofu Geoffrey K.,Awandare Gordon A.ORCID,Leal Suzanne M.

Abstract

AbstractWe investigated hearing impairment (HI) in 51 families from Ghana with at least two affected members that were negative for GJB2 pathogenic variants. DNA samples from 184 family members underwent whole-exome sequencing (WES). Variants were found in 14 known non-syndromic HI (NSHI) genes [26/51 (51.0%) families], five genes that can underlie either syndromic HI or NSHI [13/51 (25.5%)], and one syndromic HI gene [1/51 (2.0%)]. Variants in CDH23 and MYO15A contributed the most to HI [31.4% (16/51 families)]. For DSPP, an autosomal recessive mode of inheritance was detected. Post-lingual expression was observed for a family segregating a MARVELD2 variant. To our knowledge, seven novel candidate HI genes were identified (13.7%), with six associated with NSHI (INPP4B, CCDC141, MYO19, DNAH11, POTEI, and SOX9); and one (PAX8) with Waardenburg syndrome. MYO19 and DNAH11 were replicated in unrelated Ghanaian probands. Six of the novel genes were expressed in mouse inner ear. It is known that Pax8-/- mice do not respond to sound, and depletion of Sox9 resulted in defective vestibular structures and abnormal utricle development. Most variants (48/60; 80.0%) have not previously been associated with HI. Identifying seven candidate genes in this study emphasizes the potential of novel HI genes discovery in Africa.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Wellcome Trust

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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