TY - JOUR
T1 - Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families
AU - Adadey, Samuel Mawuli
AU - Wonkam-Tingang, Edmond
AU - Alves de Souza Rios, Leonardo
AU - Aboagye, Elvis Twumasi
AU - Esoh, Kevin
AU - Manyisa, Noluthando
AU - De Kock, Carmen
AU - Awandare, Gordon A.
AU - Mowla, Shaheen
AU - Wonkam, Ambroise
N1 - Publisher Copyright:
Copyright © 2022 Adadey, Wonkam-Tingang, Alves de Souza Rios, Aboagye, Esoh, Manyisa, De Kock, Awandare, Mowla and Wonkam.
PY - 2022/8/11
Y1 - 2022/8/11
N2 - We have previously reported CLIC5A and SLC12A2 variants in two families from Cameroon and Ghana, segregating non-syndromic hearing impairment (NSHI). In this study, biological assays were performed to further functionally investigate the pathogenicity of CLIC5 [c.224T>C; p.(L75P)] and SCL12A2 [c.2935G>A: p.(E979K)] variants. Ectopic expression of the proteins in a cell model shows that compared to wild-type, both the CLIC5A and SLC12A2 variants were overexpressed. The mutant CLIC5A protein appears as aggregated perinuclear bodies while the wild-type protein was evenly distributed in the cytoplasm. Furthermore, cells transfected with the wild-type CLIC5A formed thin membrane filopodia-like protrusions which were absent in the CLIC5A mutant expressing and control cells. On the other hand, the wild-type SLC12A2 expressing cells had an axon-like morphology which was not observed in the mutant expressing and control cells. A network analysis revealed that CLIC5A can interact with at least eight proteins at the base of the stereocilia. This study has generated novel biological data associated with the pathogenicity of targeted variants in CLIC5A and SLC12A2, found in two African families, and therefore expands our understanding of their pathobiology in hearing impairment.
AB - We have previously reported CLIC5A and SLC12A2 variants in two families from Cameroon and Ghana, segregating non-syndromic hearing impairment (NSHI). In this study, biological assays were performed to further functionally investigate the pathogenicity of CLIC5 [c.224T>C; p.(L75P)] and SCL12A2 [c.2935G>A: p.(E979K)] variants. Ectopic expression of the proteins in a cell model shows that compared to wild-type, both the CLIC5A and SLC12A2 variants were overexpressed. The mutant CLIC5A protein appears as aggregated perinuclear bodies while the wild-type protein was evenly distributed in the cytoplasm. Furthermore, cells transfected with the wild-type CLIC5A formed thin membrane filopodia-like protrusions which were absent in the CLIC5A mutant expressing and control cells. On the other hand, the wild-type SLC12A2 expressing cells had an axon-like morphology which was not observed in the mutant expressing and control cells. A network analysis revealed that CLIC5A can interact with at least eight proteins at the base of the stereocilia. This study has generated novel biological data associated with the pathogenicity of targeted variants in CLIC5A and SLC12A2, found in two African families, and therefore expands our understanding of their pathobiology in hearing impairment.
KW - Africa
KW - CLIC5
KW - hearing impairment
KW - hearing impairment pathobiology
KW - SLC12A2
UR - http://www.scopus.com/inward/record.url?scp=85136536916&partnerID=8YFLogxK
U2 - 10.3389/fgene.2022.924904
DO - 10.3389/fgene.2022.924904
M3 - Article
AN - SCOPUS:85136536916
SN - 1664-8021
VL - 13
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 924904
ER -