Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients.
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, RecDelta55, 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.
Laboratorio Diagnosi Pre-Postnatale Malattie Metaboliche, Istituto G.Gaslini, Genoa, Italy.
Mirella
M
Filocamo
Raffaella
R
Mazzotti
Marina
M
Stroppiano
Marco
M
Seri
Fiorina
F
Giona
Giancarlo
G
Parenti
Stefano
S
Regis
Fabio
F
Corsolini
Stefania
S
Zoboli
Rosanna
R
Gatti
D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007558:Italy; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational
D018076:DNA, Complementary; D004247:DNA; D005962:Glucosylceramidase