Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment

Simple item page
dc.contributor.authorWonkam-Tingang, Edmond
dc.contributor.authorSchrauwen, Isabelle
dc.contributor.authorEsoh, Kevin K
dc.contributor.authorBharadwaj, Thashi
dc.contributor.authorNouel-Saied, Liz M
dc.contributor.authorAcharya, Anushree
dc.contributor.authorNasir, Abdul
dc.contributor.authorAdadey, Samuel M
dc.contributor.authorMowla, Shaheen
dc.contributor.authorLeal, Suzanne M
dc.contributor.authorWonkam, Ambroise
dc.date.accessioned2021-10-12T10:59:03Z
dc.date.available2021-10-12T10:59:03Z
dc.date.issued2020-10-23
dc.date.updated2020-11-26T14:08:09Z
dc.description.abstractDNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing. We identified novel bi-allelic compound heterozygous pathogenic variants in <i>CLIC5</i>. The variants identified, i.e., the missense [NM_016929.5:c.224T&gt;C; p.(L75P)] and the splicing (NM_016929.5:c.63+1G&gt;A), were validated using Sanger sequencing in all seven available family members and co-segregated with hearing impairment (HI) in the three hearing impaired family members. The three affected individuals were compound heterozygous for both variants, and all unaffected individuals were heterozygous for one of the two variants. Both variants were absent from the genome aggregation database (gnomAD), the Single Nucleotide Polymorphism Database (dbSNP), and the UK10K and Greater Middle East (GME) databases, as well as from 122 apparently healthy controls from Cameroon. We also did not identify these pathogenic variants in 118 unrelated sporadic cases of non-syndromic hearing impairment (NSHI) from Cameroon. In silico analysis showed that the missense variant <i>CLIC5</i>-p.(L75P) substitutes a highly conserved amino acid residue (leucine), and is expected to alter the stability, the structure, and the function of the CLIC5 protein, while the splicing variant <i>CLIC5</i>-(c.63+1G&gt;A) is predicted to disrupt a consensus donor splice site and alter the splicing of the pre-mRNA. This study is the second report, worldwide, to describe <i>CLIC5</i> involvement in human hearing impairment, and thus confirms <i>CLIC5</i> as a novel non-syndromic hearing impairment gene that should be included in targeted diagnostic gene panels.en_US
dc.identifierdoi: 10.3390/genes11111249
dc.identifier.apacitationWonkam-Tingang, E., Schrauwen, I., Esoh, K. K., Bharadwaj, T., Nouel-Saied, L. M., Acharya, A., ... Wonkam, A. (2020). Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment. <i>Genes</i>, 11(11), http://hdl.handle.net/11427/35200en_ZA
dc.identifier.chicagocitationWonkam-Tingang, Edmond, Isabelle Schrauwen, Kevin K Esoh, Thashi Bharadwaj, Liz M Nouel-Saied, Anushree Acharya, Abdul Nasir, et al "Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment." <i>Genes</i> 11, 11. (2020) http://hdl.handle.net/11427/35200en_ZA
dc.identifier.citationWonkam-Tingang, E., Schrauwen, I., Esoh, K.K., Bharadwaj, T., Nouel-Saied, L.M., Acharya, A., Nasir, A. & Adadey, S.M. et al. 2020. Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment. <i>Genes.</i> 11(11) http://hdl.handle.net/11427/35200en_ZA
dc.identifier.ris TY - Journal Article AU - Wonkam-Tingang, Edmond AU - Schrauwen, Isabelle AU - Esoh, Kevin K AU - Bharadwaj, Thashi AU - Nouel-Saied, Liz M AU - Acharya, Anushree AU - Nasir, Abdul AU - Adadey, Samuel M AU - Mowla, Shaheen AU - Leal, Suzanne M AU - Wonkam, Ambroise AB - DNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing. We identified novel bi-allelic compound heterozygous pathogenic variants in <i>CLIC5</i>. The variants identified, i.e., the missense [NM_016929.5:c.224T&gt;C; p.(L75P)] and the splicing (NM_016929.5:c.63+1G&gt;A), were validated using Sanger sequencing in all seven available family members and co-segregated with hearing impairment (HI) in the three hearing impaired family members. The three affected individuals were compound heterozygous for both variants, and all unaffected individuals were heterozygous for one of the two variants. Both variants were absent from the genome aggregation database (gnomAD), the Single Nucleotide Polymorphism Database (dbSNP), and the UK10K and Greater Middle East (GME) databases, as well as from 122 apparently healthy controls from Cameroon. We also did not identify these pathogenic variants in 118 unrelated sporadic cases of non-syndromic hearing impairment (NSHI) from Cameroon. In silico analysis showed that the missense variant <i>CLIC5</i>-p.(L75P) substitutes a highly conserved amino acid residue (leucine), and is expected to alter the stability, the structure, and the function of the CLIC5 protein, while the splicing variant <i>CLIC5</i>-(c.63+1G&gt;A) is predicted to disrupt a consensus donor splice site and alter the splicing of the pre-mRNA. This study is the second report, worldwide, to describe <i>CLIC5</i> involvement in human hearing impairment, and thus confirms <i>CLIC5</i> as a novel non-syndromic hearing impairment gene that should be included in targeted diagnostic gene panels. DA - 2020-10-23 DB - OpenUCT DP - University of Cape Town IS - 11 J1 - Genes LK - https://open.uct.ac.za PY - 2020 T1 - Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment TI - Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment UR - http://hdl.handle.net/11427/35200 ER - en_ZA
dc.identifier.urihttps://doi.org/10.3390/genes11111249
dc.identifier.urihttp://hdl.handle.net/11427/35200
dc.identifier.vancouvercitationWonkam-Tingang E, Schrauwen I, Esoh KK, Bharadwaj T, Nouel-Saied LM, Acharya A, et al. Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment. Genes. 2020;11(11) http://hdl.handle.net/11427/35200.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDivision of Human Geneticsen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceGenesen_US
dc.source.journalissue11en_US
dc.source.journalvolume11en_US
dc.source.urihttps://www.mdpi.com/journal/genes
dc.titleBi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairmenten_US
dc.typeJournal Articleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
genes-11-01249.pdf
Size:
1.69 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles