Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis
Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis
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DOI：
10.1126/science.277.5333.1802
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发表时间：
1997-09-19
期刊：
影响因子：
56.9
通讯作者：
Lobel, P
中科院分区：
文献类型：
--
作者：
Sleat, DE;Donnelly, RJ;Lobel, P
典型的婴幼儿晚期神经性神经样脂褐质病（LINCL）是一种致命的神经退行性疾病，其缺陷基因仍然难以捉摸。用一种适用于其他溶酶体贮积病的方法确定了LINCL的分子基础。当使用新合成的溶酶体酶的甘露糖6-磷酸修饰作为亲和标记时，发现了LINCL中缺失的单一蛋白质。序列比较表明，该蛋白是一种胃抑素不敏感的溶酶体肽酶，并且在LINCL尸检标本中缺乏相应的酶活性。编码该蛋白的基因突变在LINCL患者中发现，但在正常对照中未发现。
Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.