Gaucher disease (GD) is characterized by a marked phenotypic and genetic diversity. It is caused by the functional deficiency of the lysosomal enzyme β-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.

高雪氏病（GD）的特征在于明显的表型和遗传多样性。它是由溶酶体酶β-葡萄糖脑苷脂酶（GCase）的功能缺陷引起的，这种缺陷在大多数情况下是由GBA1突变引起的基因和超过500种不同的致病突变已被描述。我们介绍了在过去35年中在希腊诊断出的三种类型的疾病中的141例GD病例（14例为兄弟姐妹）的生化和分子发现。111/141（78％）GD患者来自希腊。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。先前没有报道过七个突变（T231I，D283N，N462Y，LI75P，F81L，Y135S和T482K）。最常见的突变是N370S，D409H，H255Q和L444P。突变D409H; H255Q仅在希腊和阿尔巴尼亚患者中发现。仅在一个等位基因中鉴定出16个突变，包括新突变。尽管仅在1型患者中鉴定出N370S突变，但并非所有1型患者均携带此突变。我们的结果突出了高雪氏病的异质性，并支持双突变等位基因D409H; H255Q的巴尔干起源。