Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease

Nat Genet. 1993 Oct;5(2):118-23. doi: 10.1038/ng1093-118.


Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. We have cloned the human aspartoacylase (ASP) cDNA spanning 1,435 basepairs, and show that the isolated cDNA expresses aspartoacylase activity in bacteria. Furthermore, an A to C base change, at nucleotide 854, has been found in 85% of the 34 Canavan alleles tested so far. This base change results in a missense Glu285Ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. The data suggest that the catalytic centre of aspartoacylase involves a triad of Ser, His and Glu residues. Our findings have implications for diagnosis and screening of Canavan disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Canavan Disease / diagnosis
  • Canavan Disease / genetics*
  • Cattle
  • DNA, Complementary
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Sequence Alignment


  • DNA, Complementary
  • Amidohydrolases
  • aspartoacylase