title: Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia.
abstract: The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias. Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia, ataxia with vitamin E deficiency, ataxia telangiectasia, recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1 (refs. 6,7) and type 2 (ref. 8). Nonetheless, genes remain unidentified for most recessive ataxias. Additionally, pure cerebellar ataxias, which represent up to 20% of all ataxias, remain poorly studied with only two causative dominant genes being described: CACNA1A (ref. 9) and SPTBN2 (ref. 10). Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.
authors.affiliation: Centre for the Study of Brain Diseases, Université de Montréal, Montréal, Quebec, H2L 4M1, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Gros-Louis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.forename: Patrick
authors.initials: P
authors.lastname: Dion
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fox
authors.forename: Sandra
authors.initials: S
authors.lastname: Laurent
authors.forename: Steve
authors.initials: S
authors.lastname: Verreault
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bouchard
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002524:Cerebellar Ataxia / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D005820:Genetic Testing; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011792:Quebec
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human