title: New mutations in the GLA gene in Brazilian families with Fabry disease.
abstract: Fabry disease (FD) is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the alpha-galactosidase A (GLA) gene. Evaluating the enzymatic activity in male individuals usually performs the diagnosis of the disease, but in female carriers the diagnosis based only on enzyme assays is often inconclusive. In this work, we analyzed 568 individuals from 102 families with suspect of FD. Overall, 51 families presented 38 alterations in the GLA gene, among which 19 were not previously reported in literature. The alterations included 17 missense mutations, 7 nonsense mutations, 7 deletions, 6 insertions and 1 in the splice site. Six alterations (R112C, R118C, R220X, R227X, R342Q and R356W) occurred at CpG dinucleotides. Five mutations not previously described in the literature (A156D, K237X, A292V, I317S, c.1177_1178insG) were correlated with low GLA enzyme activity and with prediction of molecular damages. From the 13 deletions and insertions, 7 occurred in exons 6 or 7 (54%) and 11 led to the formation of a stop codon. The present study highlights the detection of new genomic alterations in the GLA gene in the Brazilian population, facilitating the selection of patients for recombinant enzyme-replacement trials and offering the possibility to perform prenatal diagnosis.
authors.affiliation: Department of Biophysics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: Lauro Thiago
authors.initials: LT
authors.lastname: Turaça
authors.forename: Juliana Gilbert
authors.initials: JG
authors.lastname: Pessoa
authors.forename: Fabiana Louise
authors.initials: FL
authors.lastname: Motta
authors.forename: Maria Verônica
authors.initials: MV
authors.lastname: Muñoz Rojas
authors.forename: Karen Barbosa
authors.initials: KB
authors.lastname: Müller
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Wilson
authors.initials: W
authors.lastname: Junior Marques
authors.forename: Vania
authors.initials: V
authors.lastname: D'Almeida
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: D001938:Brazil; D005091:Exons; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D022821:RNA Splice Sites; D017422:Sequence Analysis, DNA; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D000519:alpha-Galactosidase