Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon
Abstract Background Hearing impairment (HI) genes are poorly studied in African populations. Methods We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 10 individuals with HI, from four multiplex families from Cameroon, two of which were previously...
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Online Access: | https://doi.org/10.1002/mgg3.1609 |
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doaj-41244a1c9ef84194ac73ebab8f6c64f02021-08-21T11:45:29ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-03-0193n/an/a10.1002/mgg3.1609Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in CameroonAmbroise Wonkam0Kamogelo Lebeko1Shaheen Mowla2Jean Jacques Noubiap3Mike Chong4Guillaume Pare5Department of Medicine Division of Human Genetics Faculty of Health Sciences University of Cape Town Cape Town South AfricaDepartment of Medicine Division of Human Genetics Faculty of Health Sciences University of Cape Town Cape Town South AfricaDepartment of Pathology Division of Haematology Faculty of Health Sciences University of Cape Town Cape Town South AfricaCentre for Heart Rhythm Disorders South Australian Health and Medical Research Institute (SAHMRIUniversity of Adelaide and Royal Adelaide Hospital Adelaide AustraliaPopulation Health Research InstituteHamilton Health Sciences and McMaster University Hamilton ON CanadaPopulation Health Research InstituteHamilton Health Sciences and McMaster University Hamilton ON CanadaAbstract Background Hearing impairment (HI) genes are poorly studied in African populations. Methods We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 10 individuals with HI, from four multiplex families from Cameroon, two of which were previously unresolved with a targeted gene enrichment (TGE) panel of 116 genes. In silico protein modelling, western blotting and live imaging of transfected HEK293 cells were performed to study protein structure and functions. Results All PLP variants previously identified with TGE were replicated. In one previously unresolved family, we found a homozygous frameshift PLP variant in GRXCR2 (OMIM: 615762), NM_001080516.1(GRXCR2):c.251delC p.(Ile85SerfsTer33), in two affected siblings; and additionally, in 1/80 unrelated individuals affected with non‐syndromic hearing impairment (NSHI). The GRXCR2‐c.251delC variant introduced a premature stop codon, leading to truncation and loss of a zinc‐finger domain. Fluorescence confocal microscopy tracked the wild‐type GRXCR2 protein to the cellular membrane, unlike the mutated GRXCR2 protein. Conclusion This study confirms GRXCR2 as a HI‐associated gene. GRXCR2 should be included to the currently available TGE panels for HI diagnosis.https://doi.org/10.1002/mgg3.1609AfricaCameroonGRXCR2hearing impairmentwhole exome sequencing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ambroise Wonkam Kamogelo Lebeko Shaheen Mowla Jean Jacques Noubiap Mike Chong Guillaume Pare |
spellingShingle |
Ambroise Wonkam Kamogelo Lebeko Shaheen Mowla Jean Jacques Noubiap Mike Chong Guillaume Pare Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon Molecular Genetics & Genomic Medicine Africa Cameroon GRXCR2 hearing impairment whole exome sequencing |
author_facet |
Ambroise Wonkam Kamogelo Lebeko Shaheen Mowla Jean Jacques Noubiap Mike Chong Guillaume Pare |
author_sort |
Ambroise Wonkam |
title |
Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon |
title_short |
Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon |
title_full |
Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon |
title_fullStr |
Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon |
title_full_unstemmed |
Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon |
title_sort |
whole exome sequencing reveals a biallelic frameshift mutation in grxcr2 in hearing impairment in cameroon |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2021-03-01 |
description |
Abstract Background Hearing impairment (HI) genes are poorly studied in African populations. Methods We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 10 individuals with HI, from four multiplex families from Cameroon, two of which were previously unresolved with a targeted gene enrichment (TGE) panel of 116 genes. In silico protein modelling, western blotting and live imaging of transfected HEK293 cells were performed to study protein structure and functions. Results All PLP variants previously identified with TGE were replicated. In one previously unresolved family, we found a homozygous frameshift PLP variant in GRXCR2 (OMIM: 615762), NM_001080516.1(GRXCR2):c.251delC p.(Ile85SerfsTer33), in two affected siblings; and additionally, in 1/80 unrelated individuals affected with non‐syndromic hearing impairment (NSHI). The GRXCR2‐c.251delC variant introduced a premature stop codon, leading to truncation and loss of a zinc‐finger domain. Fluorescence confocal microscopy tracked the wild‐type GRXCR2 protein to the cellular membrane, unlike the mutated GRXCR2 protein. Conclusion This study confirms GRXCR2 as a HI‐associated gene. GRXCR2 should be included to the currently available TGE panels for HI diagnosis. |
topic |
Africa Cameroon GRXCR2 hearing impairment whole exome sequencing |
url |
https://doi.org/10.1002/mgg3.1609 |
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