Analysis of the Glucocerebrosidase Gene and Mutation Profile in 144 Italian Gaucher Patients
Analysis of the Glucocerebrosidase Gene and Mutation Profile in 144 Italian Gaucher Patients
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DOI：
10.1002/humu.9058
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发表时间：
2002-09-01
期刊：
影响因子：
3.9
通讯作者：
Gatti, Rosanna
中科院分区：
文献类型：
--
作者：
Filocamo, Mirella;Mazzotti, Raffaella;Gatti, Rosanna
戈谢病（GD）是最常见的溶酶体贮积病，其特征在于显著程度的临床变异性，其由葡糖脑苷脂酶基因（GBA）中的有害突变引起。在本文中，我们报告了144个无关的意大利GD患者的三种类型的疾病的分子特征。报告了意大利人的等位基因频率，并分析了突变谱。除了常见的N370 S、L444 P、RecNci I、G202 R、IVS 2 +1G>A、D409 H、F213 I突变之外，用于突变检测的不同分子策略鉴定了罕见的N107 L、R131 C、R170 C、R170 P、N188 S、S196 P、R285 C、R285 H、W312 C、D399 N、A446 P、IVS 10 -1G>A、Rec.55、全基因缺失，以及12个迄今为止仅存在于意大利人群中的突变等位基因：先前报道的R353 G、N370 S + S488 P嵌合体、IVS 8（-11delC）-14T>A）、Rec I、Y 418 C和七个新等位基因D127 X、P159 T、V214 X、T231 R、L354 X、H451 R和G202 R + M361 I。在基因型组内以及兄弟姐妹之间观察到的广泛表型差异暗示了其他修饰遗传和/或非遗传因素的显着贡献，并要求对患者进行全面评估，包括临床。，生物化学和分子生物学研究的预后，适当的干预治疗和可靠的遗传咨询。(C)2002 Wiley-Liss，Inc.
Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, Rec.55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling. (C) 2002 Wiley-Liss, Inc.