Bharadwaj Thashi, Acharya Anushree, Manyisa Noluthando Rearabetswe, Aboagye Elvis Twumasi, Peigou Wonkam Ramses, Xhakaza Lettilia, Popel Kalinka, de Kock Carmen, Schrauwen Isabelle, Wonkam Ambroise, Leal Suzanne M
Center for Statistical Genetics, Gertrude H. Sergievsky Center, and the Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Clin Genet. 2025 Nov;108(5):511-520. doi: 10.1111/cge.14765. Epub 2025 May 15.
To elucidate the genetic etiology of hearing impairment (HI) in South Africa, 45 nonsyndromic HI (NSHI) and syndromic HI (SHI) families with ≥ 2 affected members were analyzed. Exome and sanger sequencing were used to identify causal genes. For NSHI, 14 of 24 families segregated variants in NSHI genes, that is, CDH23, GJB2, MITF, MYO7A, MYO15A, PCDH15, POU3F4, REST, SLC26A4, TMPRSS3, and WFS1. For the 21 SHI families, 14 have Waardenburg syndrome, two Branchio-Oto-Renal syndromes, and one each with Bartter, Chudley-McCullough, Deafness-Albinism, MYH9-related disorder, and Pendred syndromes. The cause of SHI was determined for 14 families, with EDN3, EDNRB, GPSM2, MITF, MYH9, SLC12A1, and SLC26A4 underlying the syndrome in a single family, EYA1 in two families, and PAX3 in five families. For the NSHI and SHI genes, 52.9% and 35.7% of the variants, respectively, have not been reported in disease etiology. Additionally, two Waardenburg families segregated variants in NSHI genes, BDP1 and MYO6, but these findings need to be validated. This study enhances the understanding of the genetic landscape of HI in South Africa, revealing a high level of locus and allelic heterogeneity. Studying diverse populations provides new insights into HI etiology that, in turn, can improve genetic diagnosis and personalized management.
为阐明南非听力障碍（HI）的遗传病因，对45个有≥2名受累成员的非综合征性HI（NSHI）和综合征性HI（SHI）家庭进行了分析。采用外显子组测序和桑格测序来鉴定致病基因。对于NSHI，24个家庭中的14个家庭在NSHI基因（即CDH23、GJB2、MITF、MYO7A、MYO15A、PCDH15、POU3F4、REST、SLC26A4、TMPRSS3和WFS1）中分离出变异。对于21个SHI家庭，14个患有瓦登伯革综合征，2个患有鳃耳肾综合征，1个分别患有巴特综合征、Chudley-McCullough综合征、耳聋白化病、MYH9相关疾病和彭德莱综合征。确定了14个SHI家庭的病因，其中1个家庭综合征的病因是EDN3、EDNRB、GPSM2、MITF、MYH9、SLC12A1和SLC26A4，2个家庭是EYA1，5个家庭是PAX3。对于NSHI和SHI基因，分别有52.9%和35.7%的变异在疾病病因学中尚未见报道。此外，2个瓦登伯革家庭在NSHI基因BDP1和MYO6中分离出变异，但这些发现需要验证。本研究增进了对南非HI遗传格局的理解，揭示了高度的基因座和等位基因异质性。研究不同人群为HI病因学提供了新的见解，进而可改善基因诊断和个性化管理。
