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

Rajinder Kaul, Guang Ping Gao, Kuppareddi Balamurugan, Reuben Matalon

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Abstract

Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of Nacetylaspartic 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 - Oct 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

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