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Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients
Author(s) -
Filocamo Mirella,
Mazzotti Raffaella,
Stroppiano Marina,
Seri Marco,
Giona Fiorina,
Parenti Giancarlo,
Regis Stefano,
Corsolini Fabio,
Zoboli Stefania,
Gatti Rosanna
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9058
Subject(s) - glucocerebrosidase , biology , genetics , allele , genotype , mutation , disease , gene , genetic counseling , phenotype , mutant , molecular genetics , population , genetic heterogeneity , medicine , environmental health
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, RecΔ55, 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. © 2002 Wiley‐Liss, Inc.