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

R. Kaul, Ping Gao Guang Ping Gao, K. Balamurugan, Reuben Matalon

Research output: Contribution to journalArticle

173 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)118-123
Number of pages6
JournalNature Genetics
Volume5
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Canavan Disease
Missense Mutation
Organism Cloning
Complementary DNA
Catalytic Domain
Nucleotides
Alleles
Bacteria
aspartoacylase
Brain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. / Kaul, R.; Guang Ping Gao, Ping Gao; Balamurugan, K.; Matalon, Reuben.

In: Nature Genetics, Vol. 5, No. 2, 1993, p. 118-123.

Research output: Contribution to journalArticle

Kaul, R. ; Guang Ping Gao, Ping Gao ; Balamurugan, K. ; Matalon, Reuben. / Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. In: Nature Genetics. 1993 ; Vol. 5, No. 2. pp. 118-123.
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