Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia

Nat Genet. 2007 Jan;39(1):80-5. doi: 10.1038/ng1927. Epub 2006 Dec 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cerebellar Ataxia / genetics*
  • Cerebellum / metabolism
  • Chromosome Mapping
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Female
  • Genes, Recessive*
  • Genetic Testing
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Quebec


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SYNE1 protein, human