Discovering rare diseases: Beauce Ataxia

JAMA Neurol. 2013 Aug 19. doi: 10.1001/jamaneurol.2013.3268. [Epub ahead of print]

SYNE1 Mutations in Autosomal Recessive Cerebellar Ataxia.

Noreau A, Bourassa CV, Szuto A, Levert A, Dobrzeniecka S, Gauthier J, Forlani S, Durr A, Anheim M, Stevanin G, Brice A, Bouchard JP,Dion PA, Dupré N, Rouleau GA.

Source

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada2Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

Abstract

IMPORTANCE Autosomal recessive cerebellar ataxia type I, also known as recessive ataxia of Beauce, is a slowly progressive ataxia that leads to moderate disability with gait ataxia, dysarthria, dysmetria, mild oculomotor abnormalities, and diffuse cerebellar atrophy on brain imaging. Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene, located on chromosome 6p25, were first reported in patients who originated from a region known as "Beauce" in the province of Quebec, Canada. OBJECTIVE To better evaluate the prevalence of SYNE1 mutations in individuals with mild pure cerebellar ataxia and cerebellar atrophy, we screened the gene in additional French-Canadian (FC) families and individuals from other populations. DESIGN, SETTING, AND PARTICIPANTS Study participants were referred by their treating physician on the basis of core features of autosomal recessive cerebellar ataxia type I. After excluding individuals with known SYNE1 mutations, our cohort was composed mainly of 19 FCs and 21 individuals from other ethnic backgrounds. INTERVENTIONS Extraction of DNA from blood samples and complete resequencing of the SYNE1 gene. MAIN OUTCOMES AND MEASURES The involvement of SYNE1 mutations in individuals with ataxia worldwide by resequencing the SYNE1 gene. RESULTS Two novel truncating mutations were found among the FC participants, and 2 other novel mutations were found in a patient from France and a patient from Brazil (1 mutation each). CONCLUSIONS AND RELEVANCE This is the second report, to our knowledge, of SYNE1 gene mutations in a population other than FCs. These data suggest that mutations in SYNE1 should be investigated in families with cerebellar ataxia who live outside the FC region.