CHARACTERIZATION OF GLUCOCEREBROSIDASE IN GREEK GAUCHER DISEASE PATIENTS - MUTATION ANALYSIS AND BIOCHEMICAL-STUDIES
CHARACTERIZATION OF GLUCOCEREBROSIDASE IN GREEK GAUCHER DISEASE PATIENTS - MUTATION ANALYSIS AND BIOCHEMICAL-STUDIES
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DOI：
10.1007/bf02436006
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发表时间：
1995-01-01
影响因子：
4.2
通讯作者：
AERTS, JMFG
中科院分区：
文献类型：
--
作者：
MICHELAKAKIS, H;DIMITRIOU, E;AERTS, JMFG
戈谢病是希腊最常见的溶酶体贮积病，占雅典儿童健康研究所过去13年诊断的所有溶酶体疾病的24%。在葡萄糖脑苷脂酶基因和酶活性水平上，研究了具有非神经病性（1型）和神经病性（2型和3型）表型的希腊戈谢病患者葡萄糖脑苷脂酶缺陷的性质。在10/23名患有不同类型疾病的戈谢病患者中进行的突变分析导致鉴定出四种突变，N370 S，L444 P，R463 C和D409 H，占所研究等位基因的75%。N370 S仅与I型疾病相关。首次发现D409 H/R463 C基因型与严重的2型疾病相关。体外残留酶活性与表型或基因型之间无相关性。然而，在培养的成纤维细胞的神经病变的情况下，葡萄糖脑苷脂酶蛋白浓度降低，降解外源性C6 NBD-葡萄糖神经酰胺的能力受到更严重的损害。
Gaucher disease is the most frequent lysosomal storage disease in Greece, accounting for 24% of all lysosomal disorders diagnosed during the last 13 years at the Institute of Child Health in Athens. The nature of the defects in glucocerebrosidase in Greek Gaucher patients with non-neuronopathic (type 1) and neuronopathic (types 2 and 3) phenotypes was investigated at the level of the glucocerebrosidase gene and enzyme activity. Mutation analysis performed in 10/23 Gaucher patients with different types of the disorder led to the identification of four mutations, N370S, L444P, R463C and D409H, comprising 75% of the investigated alleles. N370S was only found in association with type I disease. The genotype D409H/R463C was identified for the first time and was associated with the severe type 2 disorder. There was no correlation between residual in vitro enzyme activity and either phenotype or genotype. However, in cultured fibroblasts of the neuronopathic cases, glucocerebrosidase protein concentration was reduced and the capacity to degrade exogenous C6NBD-glucosylceramide was more severely impaired.