title: Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease.
abstract: 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.
authors.affiliation: Research Institute, Miami Children's Hospital, Florida 33155.
authors.forename: R
authors.initials: R
authors.lastname: Kaul
authors.forename: G P
authors.initials: GP
authors.lastname: Gao
authors.forename: K
authors.initials: K
authors.lastname: Balamurugan
authors.forename: R
authors.initials: R
authors.lastname: Matalon
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017825:Canavan Disease / Q000175:diagnosis / Q000235:genetics*; D002417:Cattle; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D000581:Amidohydrolases; C019751:aspartoacylase