CLONING OF THE HUMAN ASPARTOACYLASE CDNA AND A COMMON MISSENSE MUTATION IN CANAVAN DISEASE
CLONING OF THE HUMAN ASPARTOACYLASE CDNA AND A COMMON MISSENSE MUTATION IN CANAVAN DISEASE
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DOI：
10.1038/ng1093-118
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发表时间：
1993-10-01
期刊：
影响因子：
30.8
通讯作者：
MATALON, R
中科院分区：
文献类型：
--
作者：
KAUL, R;GAO, GP;MATALON, R
Canavan病是一种常染色体隐性遗传性脑白质营养不良，是由于N-乙酰天冬氨酸酰化酶缺乏和脑内N-乙酰天冬氨酸蓄积引起的。我们已经克隆了跨越1，435个碱基对的人天冬酰化酶（ASP）cDNA，并表明分离的cDNA在细菌中表达天冬酰化酶活性。此外，到目前为止，在34个Canavan等位基因中的85%中发现了核苷酸854处的A至C碱基变化。该碱基变化导致错义Glu 285 Ala突变，该突变被预测为谷氨酸酰化酶催化结构域的一部分。这些数据表明，该酶的催化中心涉及一个三联体的丝氨酸，组氨酸和谷氨酸残基。我们的研究结果对Canavan病的诊断和筛查具有重要意义。
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.