Yalcouyé Abdoulaye, Schrauwen Isabelle, Traoré Oumou, Bamba Salia, Aboagye Elvis Twumasi, Acharya Anushree, Bharadwaj Thashi, Latanich Rachel, Esoh Kevin, Fortes-Lima Cesar A, de Kock Carmen, Jonas Mario, Maiga Alassane Dit Baneye, Cissé Cheick A K, Sangaré Moussa A, Guinto Cheick O, Landouré Guida, Leal Suzanne M, Wonkam Ambroise
Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali; Division of Human Genetics, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; McKusick-Nathans Institute, and Department of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Center for Statistical Genetics, Gertrude H. Sergievsky Center, and Department of Neurology, Columbia University Medical Center, New York, NY, USA.
HGG Adv. 2025 Jan 9;6(1):100391. doi: 10.1016/j.xhgg.2024.100391. Epub 2024 Dec 10.
Hearing impairment (HI) is the most common neurosensory disorder globally and is reported to be more prevalent in low-income countries. In high-income countries, up to 50% of congenital childhood HI is of genetic origin. However, there are limited genetic data on HI from sub-Saharan African populations. In this study, we investigated the genetic causes of HI in the Malian populations, using whole-exome sequencing. Furthermore, cDNA was transfected into HEK293T cells for localization and expression analysis in a candidate gene. Twenty-four multiplex families were enrolled, 50% (12/24) of which are consanguineous. Clustering methods showed patterns of admixture from non-African sources in some Malian populations. Variants were found in six known nonsyndromic HI (NSHI) genes, four genes that can underlie either syndromic HI (SHI) or NSHI, one SHI gene, and one novel candidate HI gene. Overall, 75% of families (18/24) were solved, and 94.4% (17/18) had variants in known HI genes including MYO15A, CDH23, MYO7A, GJB2, SLC26A4, PJVK, OTOGL, TMC1, CIB2, GAS2, PDCH15, and EYA1. A digenic inheritance (CDH23 and PDCH15) was found in one family. Most variants (59.1%, 13/22) in known HI genes were not previously reported or associated with HI. The UBFD1 candidate HI gene, which was identified in one consanguineous family, is expressed in human inner ear organoids. Cell-based experiments in HEK293T showed that mutants UBFD1 had a lower expression, compared to wild type. We report the profile of known genes and the UBFD1 candidate gene for HI in Mali and emphasize the potential of gene discovery in African populations.
听力障碍（HI）是全球最常见的神经感觉障碍，据报道在低收入国家更为普遍。在高收入国家，高达50%的先天性儿童HI是遗传起源的。然而，来自撒哈拉以南非洲人群的HI遗传数据有限。在本研究中，我们使用全外显子测序调查了马里人群中HI的遗传原因。此外，将cDNA转染到HEK293T细胞中，用于在一个候选基因中进行定位和表达分析。招募了24个多重家庭，其中50%（12/24）是近亲家庭。聚类方法显示一些马里人群中有来自非非洲来源的混合模式。在六个已知非综合征性HI（NSHI）基因、四个可导致综合征性HI（SHI）或NSHI的基因、一个SHI基因和一个新的候选HI基因中发现了变异。总体而言，75%的家庭（18/24）得到了解决，94.4%（17/18）在已知的HI基因中有变异，包括MYO15A、CDH23、MYO7A、GJB2、SLC26A4、PJVK、OTOGL、TMC1、CIB2、GAS2、PDCH15和EYA1。在一个家庭中发现了双基因遗传（CDH23和PDCH15）。已知HI基因中的大多数变异（59.1%，13/22）以前未被报道或与HI相关。在一个近亲家庭中鉴定出的UBFD1候选HI基因在人内耳类器官中表达。在HEK293T细胞中进行的基于细胞的实验表明，与野生型相比，突变体UBFD1的表达较低。我们报告了马里HI已知基因和UBFD1候选基因的概况，并强调了在非洲人群中进行基因发现的潜力。
