{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:56:06Z","timestamp":1755222966233,"version":"3.43.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin<\/jats:italic> (mHtt<\/jats:italic>) gene to the continent; however, recent work has shown the existence of a unique Htt<\/jats:italic> haplotype in South\u2010Africa specific to indigenous Africans.<\/jats:p><\/jats:sec>Objective<\/jats:title>We aimed to investigate the CAG trinucleotide repeats expansion in the Htt<\/jats:italic> gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub\u2010Saharan Africa.<\/jats:p><\/jats:sec>Methods<\/jats:title>We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first\u2010degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt<\/jats:italic>. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the mHtt<\/jats:italic> gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region.<\/jats:p><\/jats:sec>Results<\/jats:title>HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the mHTT<\/jats:italic>; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6\/21) were carriers for the mHTT;<\/jats:italic> median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD\u2014bar three who were juvenile onset of <21 years\u2014were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16\/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10\/19) than paternal transmission 36.8% (7\/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54\u201316\u00a0kya ago: Nilo\u2010Sahara and Niger\u2010Congo.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This is the first study examining HD in multiple sites in sub\u2010Saharan Africa. We demonstrated that HD is found in multiple ethnic groups residing in five sub\u2010Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio\u2010economic impact, and genetic origins need further exploration and reappraisal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12557","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T04:34:01Z","timestamp":1712032441000},"page":"149-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An exploration of the genetics of the mutant Huntingtin<\/i> (mHtt<\/i>) gene in a cohort of patients with chorea from different ethnic groups in sub\u2010Saharan Africa"],"prefix":"10.1111","volume":"89","author":[{"given":"Mendi J","family":"Muthinja","sequence":"first","affiliation":[{"name":"Huntington disease Africa Nairobi Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Othon","family":"Guelngar","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Ignace Deen University of Conakry Conakry Guinea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maouly","family":"Fall","sequence":"additional","affiliation":[{"name":"Centre Hospitalier National de Pikine Service de Neurologie Dakar Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatumah","family":"Jama","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huda Aldeen","family":"Shuja","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamila","family":"Nambafu","sequence":"additional","affiliation":[{"name":"Department of Medicine Aga Khan University Medical College of East Africa Nairobi Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Gams","family":"Massi","sequence":"additional","affiliation":[{"name":"Doula General Hospital, Faculty of Health Sciences University of Buea Buea Cameroon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oluwadamilola O.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Medicine, College of Medicine University of Lagos Lagos Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Njideka U.","family":"Okubadejo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Medicine, College of Medicine University of Lagos Lagos Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Funmilola Tolulope","family":"Taiwo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Medicine University College Hospital Ibadan Oyo Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alassane Mamadou","family":"Diop","sequence":"additional","affiliation":[{"name":"Centre Hospitalier National de Pikine Service de Neurologie Dakar Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coudjou J. D. G.","family":"de Chacus","sequence":"additional","affiliation":[{"name":"Centre Hospitalier National de Pikine Service de Neurologie Dakar Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fod\u00e9 Abass","family":"Ciss\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Ignace Deen University of Conakry Conakry Guinea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amara","family":"Ciss\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Ignace Deen University of Conakry Conakry Guinea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juzar","family":"Hooker","sequence":"additional","affiliation":[{"name":"Department of Medicine Aga Khan University Medical College of East Africa Nairobi Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilraj","family":"Sokhi","sequence":"additional","affiliation":[{"name":"Department of Medicine Aga Khan University Medical College of East Africa Nairobi Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-4449","authenticated-orcid":false,"given":"Mie","family":"Rizig","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000444020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD\u2010220529"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v15i4.23"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000835"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010019\u20101679\u20102"},{"issue":"17","key":"e_1_2_10_8_1","first-page":"685","article-title":"Huntington's chorea in a black family: A report of 2 cases","volume":"56","author":"Glass J.","year":"1979","journal-title":"South African Medical Journal"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/003591573602901120"},{"issue":"8","key":"e_1_2_10_10_1","first-page":"581","article-title":"La maladie de Huntington dans une vaste famille au sud du Togo [Huntington disease in a large family in southern Togo]","volume":"146","author":"Grunitzky E. K.","year":"1995","journal-title":"Annales De Medecine Interne"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00194305"},{"issue":"5","key":"e_1_2_10_12_1","first-page":"197","article-title":"The origin of Huntington's chorea in the Afrikaner population of South Africa","volume":"58","author":"Hayden M. R.","year":"1980","journal-title":"South African Medical Journal"},{"issue":"5","key":"e_1_2_10_13_1","first-page":"193","article-title":"The prevalence of Huntington's chorea in South Africa","volume":"58","author":"Hayden M. R.","year":"1980","journal-title":"South African Medical Journal"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.49.567.32"},{"key":"e_1_2_10_15_1","first-page":"317","article-title":"On chorea","volume":"15","author":"Huntington G.","year":"1872","journal-title":"The Medical and Surgical Reporter: A Weekly Journal"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.15.1.109"},{"issue":"12","key":"e_1_2_10_17_1","first-page":"1157","article-title":"La maladie de Huntington au Burkina Faso [Huntington disease in Burkina Faso]","volume":"156","author":"Kabore J.","year":"2000","journal-title":"Revue Neurologique"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32618"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32332"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405193302001"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10010043"},{"key":"e_1_2_10_22_1","unstructured":"Lund J. C.(1860).Chorea Sti Viti I Stersdalen. Uddrag af Distriktsoege J C Lunds Medicinalberetning for 1860. [Beretning om Sundhedstilstandenm.m. i Norge i 1860: 137\u20138. English trans. 1959]."},{"issue":"3","key":"e_1_2_10_23_1","first-page":"200","article-title":"Huntington's disease: Genetic heterogeneity in black African patients","volume":"98","author":"Magazi D. S.","year":"2008","journal-title":"South African Medical Journal"},{"issue":"1","key":"e_1_2_10_24_1","first-page":"69","article-title":"A case of Huntington's chorea in a Nigerian and the sociocultural factors associated with its diagnosis and management","volume":"35","author":"Morakinyo O.","year":"1983","journal-title":"Tropical and Geographical Medicine"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000129827.16522.78"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000106165.74751.15"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/4f8606b742ef3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt.13.18"},{"issue":"16","key":"e_1_2_10_29_1","first-page":"648","article-title":"Huntington's chorea in a black Rhodesian family","volume":"54","author":"Samuels B. 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