Brain Advance Access originally published online on May 3, 2006
Brain 2006 129(9):2332-2340; doi:10.1093/brain/awl110
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A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33–34
1 Laboratoire de neurogénétique de la motricité, Center for the study of brain diseases, Centre de recherche du CHUM Montreal, Canada 2 Clinique des maladies neuromusculaires, Centre de réadaptation Marie Enfant, CHU Mère Enfant Sainte-Justine Montreal, Canada 3 Radiology Department, Centre hospitalier de l'Université de Montréal Montreal, Canada 4 Service de neurologie, Centre hospitalier de l'Université de Sherbrooke Sherbrooke, Canada 5 Clinique des maladies neuromusculaires, Carrefour de la Santé de Jonquière Saguenay, Canada 6 Service de neurologie, Hôpital de l'Enfant-Jesus, Université Laval Quebec, QC, Canada 7 Laboratoire de neurogénétique, Center for the study of brain diseases, Centre de recherche du CHUM
Correspondence to: Bernard Brais, MD, MPhil, PhD, Laboratoire de neurogénétique de la motricité, M4211-L3, Hôpital Notre-Dame-CHUM, 1560 Sherbrooke est, Montréal, Québec, Canada, H2L 4M1 E-mail: Bernard.Brais{at}umontreal.ca
Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French–Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2–59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33–34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.
Key Words: spastic ataxia; paraplegia; founder effect; linkage; genome-wide-scan
Abbreviations: ARSACS, spastic ataxia of Charlevoix–Saguenay; ARSAL, autosomal recessive spastic ataxia with frequent leucoencephalopathy; FRDA, Friedreich ataxia; IAHSP, infantile ascending hereditary spastic paralysis; LOD, log of the odds; PCR, polymerase chain reaction; GWS, genome wide scan
Received December 13, 2005. Revised March 28, 2006. Accepted March 30, 2006.