Genomic analysis of Brazilian patients with Fabry disease
| Autor: | Ursula da Silveira Matte, Laura Bannach Jardim, Roberto Giugliani, Cristina Brinckmann Oliveira Netto, Maira Graeff Burin, Cláudia Rafaela Cecchin, Fernanda dos Santos Pereira |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male DNA Complementary Adolescent Physiology Genetic counseling Immunology Biophysics Globotriaosylceramide Ocean Engineering Biology medicine.disease_cause Polymerase Chain Reaction Biochemistry Doença de Fabry Globotriaosylceramide storage Exon chemistry.chemical_compound α-Galactosidase A medicine Humans General Pharmacology Toxicology and Pharmaceutics GLA gene X chromosome Genetics Fabry disease Mutation Genetic heterogeneity General Neuroscience Lysosomal disorders Exons Cell Biology General Medicine Middle Aged medicine.disease Pedigree chemistry alpha-Galactosidase Fabry Disease Galactosidase A Female Founder effect |
| Zdroj: | Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
| ISSN: | 1414-431X 0100-879X |
| Popis: | Fabry disease is an X-linked lysosomal disorder due to a-galactosidase A deficiency that causes storage of globotriaosylceramide. The gene coding for this lysosomal enzyme is located on the long arm of the X chromosome, in region Xq21.33-Xq22. Disease progression leads to vascular disease secondary to involvement of kidney, heart and the central nervous system. Detection of female carriers based solely on enzyme assays is often inconclusive. Therefore, mutation analysis is a valuable tool for diagnosis and genetic counseling. Many mutations of the a-galactosidase A gene have been reported with high genetic heterogeneity, being most mutations private found in only one family. The disease is panethnic, and estimates of incidence range from about 1 in 40,000 to 60,000 males. Our objective was to describe the analysis of 6 male and 7 female individuals belonging to 4 different Fabry disease families by automated sequencing of the seven exons of the alpha-galactosidase gene. Sequencing was performed using PCR fragments for each exon amplified from DNA extracted from peripheral blood. Three known mutations and one previously described in another Brazilian family were detected. Of 7 female relatives studied, 4 were carriers. Although the present study confirms the heterogeneity of mutations in Fabry disease, the finding of the same mutation previously detected in another Fabry family from our region raises the possibility of some founder effect, or genetic drift. Finally, the present study highlights the importance of molecular analysis for carrier detection and genetic counseling. |
| Databáze: | OpenAIRE |
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