New mutations in the GLA gene in Brazilian families with Fabry disease

New mutations in the GLA gene in Brazilian families with Fabry disease

Author Turaca, Lauro Thiago Autor UNIFESP Google Scholar
Pessoa, Juliana Gilbert Autor UNIFESP Google Scholar
Motta, Fabiana Louise Autor UNIFESP Google Scholar
Munoz Rojas, Maria Veronica Google Scholar
Mueller, Karen Barbosa Autor UNIFESP Google Scholar
Lourenco, Charles Marques Google Scholar
Marques, Wilson Junior Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Martins, Ana Maria Autor UNIFESP Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Genzyme Brasil
Universidade de São Paulo (USP)
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. Journal of Human Genetics (2012) 57, 347-351; doi:10.1038/jhg.2012.32; published online 3 May 2012
Keywords alpha-galactosidase A
fabry disease
Brazilian families
GLA gene
lysosomal storage disease
mutation analysis
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2008/06676-8
Date 2012-06-01
Published in Journal of Human Genetics. New York: Nature Publishing Group, v. 57, n. 6, p. 347-351, 2012.
ISSN 1434-5161 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 347-351
Access rights Closed access
Type Article
Web of Science ID WOS:000305808500002

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