Citation: Dia, Y.; Adadey, S.M.; Diop, J.P.D.; Aboagye, E.T.; Ba, S.A.; De Kock, C.; Ly, C.A.T.; Oluwale, O.G.; Sène, A.R.G.; Sarr, P.D.; et al. GJB2 Is a Major Cause of Non-Syndromic Hearing Impairment in Senegal. Biology 2022, 11, 795. https:// doi.org/10.3390/biology11050795 Academic Editor: Umberto Castiello Received: 26 April 2022 Accepted: 17 May 2022 Published: 23 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biology Article GJB2 Is a Major Cause of Non-Syndromic Hearing Impairment in Senegal Yacouba Dia 1 , Samuel Mawuli Adadey 2,3 , Jean Pascal Demba Diop 1 , Elvis Twumasi Aboagye 2 , Seydi Abdoul Ba 1 , Carmen De Kock 2 , Cheikh Ahmed Tidjane Ly 1 , Oluwafemi Gabriel Oluwale 2 , Andrea Regina Gnilane Sène 1 , Pierre Diaga Sarr 1 , Bay Karim Diallo 4 , Rokhaya Ndiaye Diallo 1 and Ambroise Wonkam 2,5, * 1 Division of Human Genetics, Faculty of Medicine, Pharmacy and Odontology, University Cheikh Anta Diop (UCAD), Dakar 10700, Senegal; yacouba.dia@ucad.edu.sn (Y.D.); jeanpascaldemba.diop@ucad.edu.sn (J.P.D.D.); banourrou@gmail.com (S.A.B.); cheikh9611@gmail.com (C.A.T.L.); andreareginagnilane.sene@ucad.edu.sn (A.R.G.S.); lordpeter.mcsarr@gmail.com (P.D.S.), rokhaya.ndiaye@ucad.edu.sn (R.N.D.) 2 Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; smadadey@st.ug.edu.gh (S.M.A.); etaoagye@st.ug.edu.gh (E.T.A.); carmen.dekock@uct.ac.za (C.D.K.); femi.oluwole@gmail.com (O.G.O.) 3 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana 4 Department of Oto-Rhino-Laryngology, Albert Royer Children’s Hospital, Dakar 10700, Senegal; bayiallo@yahoo.fr 5 McKusick-Nathans Institute and Department of Genetic Medicine, Johns-Hopskins University School of Medicine, Baltimore, MD 21205, USA * Correspondence: awonkam1@jhmi.edu; Tel.: +27-21-4066-307 or +1-443-287-0245 Simple Summary: The prevalence of GJB2-related (MIM: 121011) congenital non-syndromic hear- ing impairment (NSHI) accounts for close to 50% in populations of Asian and European ancestry. However, in sub-Saharan Africa, except for Ghana, previous data showed that the prevalence of GJB2-associated NSHI is close to zero. To investigate the contribution of GJB2 mutations in autosomal recessive NSHI in Senegal, we screened 129 affected and 143 unaffected individuals from 44 multiplex families, 9 sporadic cases, and 148 hearing controls with no personal or family history of hearing impairment, by targeted gene sequencing. We identified three pathogenic GJB2 variants in 34% (n = 15/44) of multiplex families, of which 80% (n = 12/15) were consanguineous. The most common variant, GJB2: c.94C>T: p.(Arg32Cys), accounted for 27.3% (n = 12/44) of familial cases. We also identified the previously reported “Ghanaian” founder variant, GJB2: c.427C>T: p.(Arg143Trp), in four multiplex Senegalese families. Relatively high allele frequencies of c.94C>T. and c.427C>T vari- ants were observed among the screened hearing controls: 1% (n = 2/148 ∗ 2), and 2% (n = 4/148 ∗ 2), respectively. No GJB6-D13S18 deletion was identified in any of the hearing-impaired participants. The data suggest that GJB2: c.94C>T: p.(Arg32Cys) should be routinely tested in NSHI in Senegal. Abstract: This study aimed to investigate GJB2 (MIM: 121011) and GJB6 (MIM: 604418) variants associated with familial non-syndromic hearing impairment (HI) in Senegal. We investigated a total of 129 affected and 143 unaffected individuals from 44 multiplex families by segregating autosomal recessive non-syndromic HI, 9 sporadic HI cases of putative genetic origin, and 148 control individuals without personal or family history of HI. The DNA samples were screened for GJB2 coding-region variants and GJB6-D3S1830 deletions. The mean age at the medical diagnosis of the affected individuals was 2.93 ± 2.53 years [range: 1–15 years]. Consanguinity was present in 40 out of 53 families (75.47%). Variants in GJB2 explained HI in 34.1% (n = 15/44) of multiplex families. A bi-allelic pathogenic variant, GJB2: c.94C>T: p.(Arg32Cys) accounted for 25% (n = 11/44 families) of familial cases, of which 80% (n = 12/15) were consanguineous. Interestingly, the previously reported “Ghanaian” founder variant, GJB2: c.427C>T: p.(Arg143Trp), accounted for 4.5% (n = 2/44 families) of the families investigated. Among the normal controls, the allele frequency of GJB2: c.94C>T and GJB2: c.427C>T was estimated at 1% (2/148 ∗ 2) and 2% (4/148 ∗ 2), respectively. No GJB6-D3S1830 Biology 2022, 11, 795. https://doi.org/10.3390/biology11050795 https://www.mdpi.com/journal/biology