Prevalence of dentatorubral-pallidoluysian atrophy in a large series of white patients with cerebellar ataxia.
BACKGROUND
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder mainly diagnosed in Japan. Its prevalence is low in other countries. Three phenotypes are described: choreoathetoid movements, cerebellar ataxia, and progressive myoclonic epilepsy.


OBJECTIVE
To evaluate the frequency of DRPLA in European patients with sporadic or autosomal dominant cerebellar ataxia.


METHODS
We analyzed a series of 809 index patients with either autosomal dominant cerebellar ataxia (416 families) or progressive cerebellar ataxia without a family history of the disease (393 cases) for the DRPLA mutation.


RESULTS
We identified a CAG repeat expansion in the DRPLA gene in one family and in one patient without a family history. The familial case illustrates the phenomenon of anticipation and the previously established correlation between the phenotype and size of the expansion. A censored-history family or expansion of large normal CAG repeats during paternal transmission could be implicated in the patient without a family history.


CONCLUSIONS
This study enables us to estimate the frequency of the disease as 0.25% in both families with autosomal dominant cerebellar ataxia and sporadic cases of ataxia in our series, confirming the very low frequency of DRPLA in Europe. In both familial and sporadic cases, molecular testing for DRPLA could be restricted to patients with ataxia with one of the following features: chorea, dementia, or myoclonic epilepsy.
Le Ber
Isabelle
I
Institut National de la Santé et de la Recherche Médicale U289, Fédération de Neurologie, Hôpital Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47 boulevard de l'Hôpital, 75651 Paris CEDEX 13, France.
Camuzat
Agnès
A
Castelnovo
Giovanni
G
Azulay
Jean-Philippe
JP
Genton
Pierre
P
Gastaut
Jean-Louis
JL
Broglin
Dominique
D
Labauge
Pierre
P
Brice
Alexis
A
Durr
Alexandra
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000150:complications / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020191:Myoclonic Epilepsies, Progressive / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D018911:Trinucleotide Repeats; D044465:White People
D009419:Nerve Tissue Proteins; C095278:atrophin-1