A South African mixed ancestry family with Huntington disease-like 2: Clinical and genetic features

Huntington disease‐like 2 (HDL2) is a neurodegenerative disorder caused by an expansion of a CTG repeat in the junctophilin‐3 gene (JPH3). A limited number of HDL2 families have been reported, all of apparently Black African ancestry. We report on a South African family that presented with progressi...

Full description

Saved in:
Bibliographic Details
Published in:Movement disorders 2007-10, Vol.22 (14), p.2083-2089
Main Authors: Bardien, Soraya, Abrahams, Fatima, Soodyall, Himla, van der Merwe, Lize, Greenberg, Jacquie, Brink, Tinus, Carr, Jonathan
Format: Article
Language:English
Subjects:
Adult
Age of Onset
Biological and medical sciences
Brain - pathology
CTG repeats
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Family Health
Female
genetic ancestry
HDL2 phenotype
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Huntington Disease - epidemiology
Huntington Disease - genetics
Huntington Disease - pathology
Huntington Disease - physiopathology
Huntington disease-like 2
JPH3
Magnetic Resonance Imaging - methods
Male
Medical sciences
Membrane Proteins - genetics
Middle Aged
Nervous system (semeiology, syndromes)
Neurology
South Africa - epidemiology
South Africa - ethnology
Trinucleotide Repeat Expansion - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Huntington disease‐like 2 (HDL2) is a neurodegenerative disorder caused by an expansion of a CTG repeat in the junctophilin‐3 gene (JPH3). A limited number of HDL2 families have been reported, all of apparently Black African ancestry. We report on a South African family that presented with progressive dementia and a movement disorder affecting numerous family members. Genotyping of the JPH3 CTG repeat revealed pathogenic expansions in three affected individuals. Whereas HDL2 is thought to be clinically indistinguishable from Huntington disease (HD), 2 of the patients in this study presented with clinical symptoms that differed substantially from HD; one had myoclonus and the other had Parkinsonism. Moreover, brain magnetic resonance imaging scans of these patients showed imaging features atypical for HD. Mitochondrial DNA and Y‐chromosome DNA analysis on a family member showed that his maternal and paternal ancestries are typical of that found among the South African mixed ancestry or colored population. A difference in the distribution of CTG repeats between Caucasian and Black individuals was detected. We conclude that the phenotype of HDL2 is broad and can differ from that of typical HD. The diagnosis therefore should be considered in a wide spectrum of neuropsychiatric and abnormal movement presentations. © 2007 Movement Disorder Society
ISSN:0885-3185
1531-8257
DOI:10.1002/mds.21672