Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.
Am. J. Med. Genet.. 2015-06-16; 168(7): 573-585
DOI: 10.1002/ajmg.b.32332
Lire sur PubMed
1. Am J Med Genet B Neuropsychiatr Genet. 2015 Oct;168(7):573-85. doi:
10.1002/ajmg.b.32332. Epub 2015 Jun 16.
Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2
(HDL2) are common in South African patients with African ancestry and a
Huntington disease phenotype.
Krause A(1)(2), Mitchell C(1), Essop F(1)(2), Tager S(3)(4), Temlett J(3)(5),
Stevanin G(6)(7), Ross C(8), Rudnicki D(9), Margolis R(10).
Author information:
(1)Division of Human Genetics, National Health Laboratory Service, Johannesburg,
South Africa.
(2)Division of Human Genetics, School of Pathology, Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, South Africa.
(3)Department of Neurology, University of the Witwatersrand, Johannesburg, South
Africa.
(4)Donald Gordon Medical Centre, Johannesburg, South Africa.
(5)Department Clinical Neurology, University of Adelaide and the Royal Adelaide
Hospital, Adelaide, Australia.
(6)Sorbonne Universités, UPMC Univ Paris, Institut du Cerveau et de la Moelle
épinière, Paris, France.
(7)Ecole Pratique des Hautes Etudes, Paris, France.
(8)Johns Hopkins University School of Medicine, Departments of Psychiatry,
Neurology, Neuroscience, and Pharmacology and Molecular Sciences and Program in
Cellular and Molecular Medicine, Baltimore, Maryland.
(9)Johns Hopkins University School of Medicine, Departments of Psychiatry and
Program in Cellular and Molecular Medicine, Baltimore, Maryland.
(10)Johns Hopkins University School of Medicine, Departments of Psychiatry and
Neurology and Program in Cellular and Molecular Medicine, Baltimore, Maryland.
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 huntingtin (HTT) gene on
chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on
chromosome 16q24.2 causes a Huntington disease-like 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 JPH3 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 HTT. However, 15% (20/130) of black South African patients and no
white patients (0/171) had an expansion in JPH3, 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. JPH3 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 JPH3
mutations.
© 2015 Wiley Periodicals, Inc.
DOI: 10.1002/ajmg.b.32332
PMCID: PMC4565761
PMID: 26079385 [Indexed for MEDLINE]