{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:03:47Z","timestamp":1790964227431,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T00:00:00Z","timestamp":1434412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH NS16375, NIH NS078643, NS075825, and NS064138"],"award-info":[{"award-number":["NIH NS16375, NIH NS078643, NS075825, and NS064138"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the <jats:italic>huntingtin<\/jats:italic> (<jats:italic>HTT<\/jats:italic>) gene on chromosome 4p. A CAG\/CTG repeat expansion in the <jats:italic>junctophilin\u20103<\/jats:italic> (<jats:italic>JPH3<\/jats:italic>) gene on chromosome 16q24.2 causes a Huntington disease\u2010like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the <jats:italic>JPH3<\/jats:italic> mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106\/171) of white patients compared to only 36% (47\/130) of black patients had an expansion in <jats:italic>HTT<\/jats:italic>. However, 15% (20\/130) of black South African patients and no white patients (0\/171) had an expansion in <jats:italic>JPH3<\/jats:italic>, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. <jats:italic>JPH3<\/jats:italic> haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for <jats:italic>JPH3<\/jats:italic> mutations. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32332","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T13:33:39Z","timestamp":1434461619000},"page":"573-585","source":"Crossref","is-referenced-by-count":54,"title":["Junctophilin 3 (<i>JPH3<\/i>) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype"],"prefix":"10.1002","volume":"168","author":[{"given":"Amanda","family":"Krause","sequence":"first","affiliation":[{"name":"Division of Human Genetics National Health Laboratory Service Johannesburg South Africa"},{"name":"Division of Human Genetics School of Pathology Faculty of Health Sciences University of the Witwatersrand Johannesburg South 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