Cargando…
Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families
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....
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403182/ https://www.ncbi.nlm.nih.gov/pubmed/36035115 http://dx.doi.org/10.3389/fgene.2022.924904 |
_version_ | 1784773315224666112 |
---|---|
author | Adadey, Samuel Mawuli Wonkam-Tingang, Edmond Alves de Souza Rios, Leonardo Aboagye, Elvis Twumasi Esoh, Kevin Manyisa, Noluthando De Kock, Carmen Awandare, Gordon A. Mowla, Shaheen Wonkam, Ambroise |
author_facet | Adadey, Samuel Mawuli Wonkam-Tingang, Edmond Alves de Souza Rios, Leonardo Aboagye, Elvis Twumasi Esoh, Kevin Manyisa, Noluthando De Kock, Carmen Awandare, Gordon A. Mowla, Shaheen Wonkam, Ambroise |
author_sort | Adadey, Samuel Mawuli |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9403182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94031822022-08-26 Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families Adadey, Samuel Mawuli Wonkam-Tingang, Edmond Alves de Souza Rios, Leonardo Aboagye, Elvis Twumasi Esoh, Kevin Manyisa, Noluthando De Kock, Carmen Awandare, Gordon A. Mowla, Shaheen Wonkam, Ambroise Front Genet Genetics 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. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9403182/ /pubmed/36035115 http://dx.doi.org/10.3389/fgene.2022.924904 Text en Copyright © 2022 Adadey, Wonkam-Tingang, Alves de Souza Rios, Aboagye, Esoh, Manyisa, De Kock, Awandare, Mowla and Wonkam. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Adadey, Samuel Mawuli Wonkam-Tingang, Edmond Alves de Souza Rios, Leonardo Aboagye, Elvis Twumasi Esoh, Kevin Manyisa, Noluthando De Kock, Carmen Awandare, Gordon A. Mowla, Shaheen Wonkam, Ambroise Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title | Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title_full | Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title_fullStr | Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title_full_unstemmed | Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title_short | Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families |
title_sort | cell-based analysis of clic5a and slc12a2 variants associated with hearing impairment in two african families |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403182/ https://www.ncbi.nlm.nih.gov/pubmed/36035115 http://dx.doi.org/10.3389/fgene.2022.924904 |
work_keys_str_mv | AT adadeysamuelmawuli cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT wonkamtingangedmond cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT alvesdesouzariosleonardo cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT aboagyeelvistwumasi cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT esohkevin cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT manyisanoluthando cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT dekockcarmen cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT awandaregordona cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT mowlashaheen cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies AT wonkamambroise cellbasedanalysisofclic5aandslc12a2variantsassociatedwithhearingimpairmentintwoafricanfamilies |