Alfonso Pilar, Aznarez Sofía, Giralt Manuel, Pocovi Miguel, Giraldo Pilar
Departamento de Bioquímica y Biología Molecular y Celular, Facultad Ciencias, Universidad de Zaragoza, Plaza San Francisco s/n, 50009, Zaragoza, Spain.
Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain.
J Hum Genet. 2007;52(5):391-396. doi: 10.1007/s10038-007-0135-4. Epub 2007 Apr 11.
Mutations in the glucocerebrosidase (GBA) gene cause Gaucher disease (GD). The aim of this study was to characterise the GBA mutations and analyze genotype/phenotype relationships in 193 unrelated patients from the Spanish GD Registry. We have identified 98.7% of the mutated GBA alleles, finding 56 different GBA mutations and 66 genotypes causing GD in Spain: 47 previously described mutations and 9 novel mutations (4 missense R395C, R463H, W312R and V398I, 1 nonsense R359X, 4 frameshift c.708delC, c.1214-1215delGC, c.1439-1445del7 and c.42-65del24). The most prevalent mutations were N370S and L444P, accounting for 68.7% of the mutated alleles. A wide phenotypic difference was observed within each genotypic group, and 9% of diagnosed type 1 patients developed neurological involvement including parkisonism, tremor, hypoacusia and eye movements. All of these findings indicate that there is a significant genotypic heterogeneity that explains the huge phenotypic variation among Spanish GD patients.
葡萄糖脑苷脂酶（GBA）基因突变会导致戈谢病（GD）。本研究的目的是对193名来自西班牙戈谢病登记处的非亲属患者的GBA突变进行特征分析，并分析基因型/表型关系。我们已鉴定出98.7%的GBA突变等位基因，在西班牙发现了56种不同的GBA突变和66种导致戈谢病的基因型：47种先前已描述的突变和9种新突变（4种错义突变R395C、R463H、W312R和V398I，1种无义突变R359X，4种移码突变c.708delC、c.1214 - 1215delGC、c.1439 - 1445del7和c.42 - 65del24）。最常见的突变是N370S和L444P，占突变等位基因的68.7%。在每个基因型组中都观察到了广泛的表型差异，9%被诊断为1型的患者出现了神经受累，包括帕金森综合征、震颤、听力减退和眼球运动异常。所有这些发现表明存在显著的基因型异质性，这解释了西班牙戈谢病患者之间巨大的表型差异。
