Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece
Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece
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DOI：
10.1016/j.ymgmr.2020.100614
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发表时间：
2020-09-01
影响因子：
1.9
通讯作者：
Michelakakis, Helen
中科院分区：
文献类型：
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作者：
Dimitriou, Evangelia;Moraitou, Marina;Michelakakis, Helen
戈谢病（GD）的特点是一个显着的表型和遗传多样性。它是由溶酶体酶β-葡糖脑苷脂酶（GCase）的功能缺陷引起的，在大多数情况下，这是由GBA 1基因突变引起的，已经描述了超过500种不同的致病突变。我们目前的生化和分子生物学研究结果在141例GD（14个兄弟姐妹）与三种类型的疾病诊断在希腊在过去的35年。111/141（78%）例GD患者为希腊裔。其余患者为阿尔巴尼亚人（24/141; 17%）、叙利亚人（2/141; 1.4%）、埃及人（2/141; 1.4%）、意大利人（1/141; 0.7%）和波兰人（1/141; 0.7%）。突变分析确定了28种不同的突变和37种不同的基因型。其中7个突变以前未报道（T231 I，D283 N，N462 Y，LI 75 P，F81 L，Y135 S和T482 K）。最常见的突变是N370 S、D409 H、H255 Q和L444 P。突变D409 H; H255 Q仅在希腊和阿尔巴尼亚患者中发现。16个突变，包括新的突变，只在一个等位基因中被发现。虽然N370 S突变仅在1型患者中发现，但并非所有1型患者都携带这种突变。我们的研究结果突出了戈谢病的异质性，并支持双突变等位基因D409 H; H255 Q的巴尔干半岛的起源。
Gaucher disease (GD) is characterized by a marked phenotypic and genetic diversity. It is caused by the functional deficiency of the lysosomal enzyme beta-glucocerebrosidase (GCase), which in most instances results from mutations in the GBA1 gene and over 500 different disease causing mutations have been described. We present the biochemical and molecular findings in 141 GD cases (14 were siblings) with the three types of the disorder diagnosed in Greece over the last 35 years. 111/141 (78%) GD patients were of Greek origin. The remaining patients were Albanian (24/141; 17%), Syrian (2/141; 1.4%), Egyptian (2/141; 1.4%), Italian (1/141; 0.7%) and Polish (1/141; 0.7%). Mutation analysis identified 28 different mutations and 37 different genotypes. Seven of the mutations were not previously reported (T231I, D283N, N462Y, LI75P, F81L, Y135S and T482K). The most frequent mutations were N370S, D409H;H255Q and L444P. Mutation D409H;H255Q was only identified in Greek and Albanian patients. Sixteen mutations, including the novel ones, were identified only in one allele. Although the N370S mutation was identified only in type 1 patients, not all of type 1 patients carried this mutation. Our results highlight the heterogeneity of Gaucher disease and support the Balkan origin of the double mutant allele D409H;H255Q.