TY - JOUR
T1 - Exome sequencing of families from Ghana reveals known and candidate hearing impairment genes
AU - Wonkam, Ambroise
AU - Adadey, Samuel Mawuli
AU - Schrauwen, Isabelle
AU - Aboagye, Elvis Twumasi
AU - Wonkam-Tingang, Edmond
AU - Esoh, Kevin
AU - Popel, Kalinka
AU - Manyisa, Noluthando
AU - Jonas, Mario
AU - deKock, Carmen
AU - Nembaware, Victoria
AU - Cornejo Sanchez, Diana M.
AU - Bharadwaj, Thashi
AU - Nasir, Abdul
AU - Everard, Jenna L.
AU - Kadlubowska, Magda K.
AU - Nouel-Saied, Liz M.
AU - Acharya, Anushree
AU - Quaye, Osbourne
AU - Amedofu, Geoffrey K.
AU - Awandare, Gordon A.
AU - Leal, Suzanne M.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - We 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.
AB - We 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.
UR - http://www.scopus.com/inward/record.url?scp=85128391767&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03326-8
DO - 10.1038/s42003-022-03326-8
M3 - Article
C2 - 35440622
AN - SCOPUS:85128391767
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 369
ER -