{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:32:23Z","timestamp":1774956743702,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107755Z\/15\/Z"],"award-info":[{"award-number":["107755Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NHGRI), USA","award":["U01-HG-009716"],"award-info":[{"award-number":["U01-HG-009716"]}]},{"name":"African Academy of Science\/Wellcome Trust","award":["H3A\/18\/001"],"award-info":[{"award-number":["H3A\/18\/001"]}]},{"name":"National Institute of Deafness and other Communication Disorders","award":["R01 DC01165, DC003594 and DC016593"],"award-info":[{"award-number":["R01 DC01165, DC003594 and DC016593"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 CLIC5. 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 CLIC5-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 CLIC5-(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 CLIC5 involvement in human hearing impairment, and thus confirms CLIC5 as a novel non-syndromic hearing impairment gene that should be included in targeted diagnostic gene panels.<\/jats:p>","DOI":"10.3390\/genes11111249","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T08:59:28Z","timestamp":1603443568000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment"],"prefix":"10.3390","volume":"11","author":[{"given":"Edmond","family":"Wonkam-Tingang","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6082","authenticated-orcid":false,"given":"Isabelle","family":"Schrauwen","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4024-5681","authenticated-orcid":false,"given":"Kevin K.","family":"Esoh","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-5655","authenticated-orcid":false,"given":"Thashi","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-7788","authenticated-orcid":false,"given":"Liz M.","family":"Nouel-Saied","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anushree","family":"Acharya","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-3500","authenticated-orcid":false,"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-2786","authenticated-orcid":false,"given":"Samuel M.","family":"Adadey","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"},{"name":"West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra LG 54, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6802-0495","authenticated-orcid":false,"given":"Shaheen","family":"Mowla","sequence":"additional","affiliation":[{"name":"Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne M.","family":"Leal","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-9051","authenticated-orcid":false,"given":"Ambroise","family":"Wonkam","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2471\/BLT.13.128728","article-title":"The global burden of disabling hearing impairment: A call to action","volume":"92","author":"Olusanya","year":"2014","journal-title":"Bull. 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