title: Detection of 12 new mutations in Gaucher disease Brazilian patients.
abstract: Gaucher disease is the most frequent lysosome storage disease and presents an autosomal recessive mode of inheritance. It is caused by mutations at the GBA gene leading to deficient activity of the glucocerebrosidase enzyme. This report describes 12 new mutations [c.38A>G (K-27R), c.220G>A (G35S), c.448G>A (E111K), IVS4+1G>A, c.746C>T (A210V), c.776A>G (Y220C), c.793delC (Q226_fs4X), c.1102C>T (R329C), c.1300C>T (R395C), c.1309G>A (V398I), c.1324-1326delATT (delI403) and c.1583T>C (I489T)] and 4 novel silent alterations [c.342C>T (F75), c.528C>T (D137), c.1011C>T (D298) and c.1092G>A (G325)] detected among 40 unrelated Brazilian type 1 Gaucher disease patients by a combination of RFLP, dHPLC and DNA sequencing procedures. The R329C mutation, previously described in a Parkinson's disease patient (A. Lwin, E. Orvisky, O. Goker-Alpan, M.E. LaMarca, E. Sidransky. Glucocerebrosidase mutations in subjects with Parkinsonism. Mol. Genet. Metab. 81 (2004) 70-73), is described here for the first time in a Gaucher disease patient. Several genotype-phenotype correlations could be established, contributing significantly to the panel of reported mutations and conferring predictive value to their detection.
authors.affiliation: Depto de Genética e Biologia Evolutiva, Instituto de Biociências-Universidade de São Paulo, R. do Matão 277, sala 350, São Paulo-SP CEP: 05508-900, Brazil. robertor@usp.br
authors.forename: R
authors.initials: R
authors.lastname: Rozenberg
authors.forename: D C
authors.initials: DC
authors.lastname: Fox
authors.forename: E
authors.initials: E
authors.lastname: Sobreira
authors.forename: L V
authors.initials: LV
authors.lastname: Pereira
mesh_terms: D001938:Brazil; D004252:DNA Mutational Analysis; D005260:Female; D005776:Gaucher Disease / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005962:Glucosylceramidase