Browsing by Author "Aboagye, Elvis Twumasi"

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    Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations
    (2022-03-21) Aboagye, Elvis Twumasi; Adadey, Samuel Mawuli; Esoh, Kevin; Jonas, Mario; de Kock, Carmen; Amenga-Etego, Lucas; Awandare, Gordon A; Wonkam, Ambroise
    Gap junction protein beta 2 (GJB2) (connexin 26) variants are commonly implicated in non-syndromic hearing impairment (NSHI). In Ghana, the GJB2 variant p.(Arg143Trp) is the largest contributor to NSHI and has a reported prevalence of 25.9% in affected multiplex families. To date, in the African continent, GJB2-p.(Arg143Trp) has only been reported in Ghana. Using wholeexome sequencing data from 32 individuals from 16 families segregating NSHI, and 38 unrelated hearing controls with the same ethnolinguistic background, we investigated the date and origin of p.(Arg143Trp) in Ghana using linked markers. With a Bayesian linkage disequilibrium gene mapping method, we estimated GJB2-p.(Arg143Trp) to have originated about 9625 years (385 generations) ago in Ghana. A haplotype analysis comparing data extracted from Ghanaians and those from the 1000 Genomes project revealed that GJB2-p.(Arg143Trp) is carried on different haplotype backgrounds in Ghanaian and Japanese populations, as well as among populations of European ancestry, lending further support to the multiple independent origins of the variant. In addition, we found substantial haplotype conservation in the genetic background of Ghanaian individuals with biallelic GJB2- p.(Arg143Trp) compared to the GJB2-p.(Arg143Trp)-negative group with normal hearing from Ghana, suggesting a strong evolutionary constraint in this genomic region in Ghanaian populations that are homozygous for GJB2-p.(Arg143Trp). The present study evaluates the age of GJB2-p.(Arg143Trp) at 9625 years and supports the multiple independent origins of this variant in the global population.
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    Genetics of Waardenburg Syndrome in Africa: A Systematic Review
    (2025-12-22) Aboagye, Elvis Twumasi; Wonkam, Ramses Peigou; de Kock, Carmen; Dandara, Collet; Wonkam, Ambroise
    Waardenburg syndrome (WS) represents a group of genetic conditions characterized by auditory and pigmentation defects. Pathogenic variants in PAX3, MITF, SOX10, EDN3, EDNRB, SNAI2, and KITLG genes have been associated with WS across multiple populations; a comprehensive study of WS in Africa has not yet been reported. We conducted a systematic review of clinical expressions and genetics of WS across Africa. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and the study protocol was registered on PROSPERO, the International Prospective Register of Systematic Reviews (2025 CRD420250655744). A literature search was performed on Google Scholar, PubMed, Scopus, Directory of Open Access Journals (DOAJ), Global Index Medicus, African-Wide Information, ScienceDirect, Connecting Repositories (CORE), and the Web of Science databases. We reviewed a total of 15 articles describing 84 WS cases, which showed no gender bias and a mean age at reporting of 17.5 years. Congenital, sensorineural, and profound hearing loss was described in most cases (66.7%; n = 56/84). WS type 2 (WS2), with characteristically no dystopia canthorum, is the predominant subtype (36.9%; n = 31/84). Pathogenic variants in four WS known genes, i.e., PAX3 (13 families), SOX10 (7 families), EDNRB (4 families), and EDN3 (1 family), were reported in Morocco, Tunisia, and South Africa. One candidate gene (PAX8) was described in one family in Ghana. Two non-syndromic hearing loss (NSHL) genes (BDP1 and MYO6) were reported in two separate families in South Africa, suggesting a possible phenotypic expansion. The highest number of WS cases was described in South Africa (38.1%; n = 32/84) and Tunisia (26.2%; n = 22/84). Gene variants were missense (27/43), deletion (7/43), splicing (5/43), nonsense (2/43), indel (1/43), and duplication (1/43), chiefly segregating in an autosomal dominant inheritance mode. There was no functional data to support the pathogenicity of putative causative variants. This review showed that WS2 is the most common in Africa. Variants in PAX3 and SOX10 were the predominant genetic causes. This study emphasizes the need to further investigate in-depth clinical characterization, molecular landscape, and the pathobiology of WS in Africa.