CHOREA-ACANTHOCYTOSIS (ChAc) IN FRENCH CANADIANS: FOUNDER EFFECT, SEIZURE CHARACTERISATION AND GENOTYPE-PHENOTYPE CORRELATIONS

Frederick Andermann, Anna Jansen, François Dubeau, S. Chouinard, Francine Robert, A. Lang, C. Dobson-Stone, Adrian Danek, Anthony Monaco, E Andermann, The International League Against Epilepsy (Redacteur)

Onderzoeksoutput: Meeting abstract (Journal)

Samenvatting

Purpose: To characterise the clinical and molecular findings in French
Canadian (FC) families with chorea-acanthocytosis, and to determine
genotype-phenotype correlations.
Method:We ascertained 12 affected individuals in four families. Detailed
medical and family histories were obtained. EEG, video-telemetry,
brain MRI with volumetric studies of the amygdala and hippocampus, as
well as neuropsychological testing were performed. Blood smears were
examined for acanthocytes, and CK levels were determined. Field trips
in two families yielded over 175 blood samples for mutation analysis.
Results: All families originated from Quebec. There was parental
consanguinity in 4 of 6 affected sibships, and probably in a fifth. Epilepsy
was a prominent feature, although family members had very diverse
clinical manifestations, including tics, chorea, psychosis and dementia.
Seizures preceded the onset of movement disorders by up to 15 years.
Most seizures were suggestive of mesial temporal onset. EEGs showed
temporal or bitemporal epileptic discharges and seizure onsets. There
was no evidence for hippocampal atrophy. Seven affected individuals
were homozygous for a deletion including exons 70-73 of VPS13A and
exons 6-7 of GNA14 (EX70-EX73del). These patients shared a common
haplotype in the same region. Two affected sisters were homozygous for
a splice mutation 4242 + 1G > T, whereas their 2 male cousins were
heterozygous for EX70-EX73del and 4242 + 1 G>T. Of 9 patients with
the deletion, including 2 heterozygotes, 7 had epilepsy (77%). The 2
sisters with the splice mutation did not develop seizures.
Conclusion: The identification of a common 9q21 haplotype associated
with EX70-EX73del in 4 apparently unrelated FC ChAc families
implies a founder effect. Routine testing for EX70-EX73del in suspected
ChAc cases may be worthwhile in this population. Genotype-phenotype
correlation suggests that the deletion mutation is strongly associated with
epilepsy.
Originele taal-2English
Pagina's (van-tot)85-85
Aantal pagina's1
TijdschriftEpilepsia
Volume47
StatusPublished - 2006
Evenement7th European Congress on Epileptology - Helsinki, Finland
Duur: 2 jul 20066 jul 2006

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The International League Against Epilepsy

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