Estamos realizando la búsqueda. Por favor, espere...

 Detalle_Publicacion

Increased glycolipid storage produced by the inheritance of a complex intronic haplotype in the ?-galactosidase A (GLA) gene

Abstract: BACKGROUND: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of ?-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.-10C > T, c.369 + 990C > A, c.370-81_370-77delCAGCC, c.640-16A > G, c.1000-22C > T) within the GLA gene associated with Fabry-like symptoms and galactosphingolipid accumulation. We analysed ?-Gal A activity in plasma, leukocytes and skin fibroblasts in patients, and measured accumulation of galactosphingolipids by enzymatic methods and immunofluorescence techniques. Additionally, we evaluated GLA expression using quantitative PCR, EMSA, and cDNA cloning. RESULTS: CIH carriers had an altered GLA expression pattern, although most of the carriers had high residual enzyme activity in plasma, leukocytes and in skin fibroblasts. Nonetheless, CIH carriers had significant galactosphingolipid accumulation in fibroblasts in comparison with controls, and also glycolipid deposits in renal tubules and glomeruli. EMSA assays indicated that the c.-10C > T variant in the promoter affected a nuclear protein binding site. CONCLUSIONS: Thus, inheritance of the CIH caused an mRNA deregulation altering the GLA expression pattern, producing a tissue glycolipid storage

 Fuente: BMC Genet. 2015 Sep 3;16:109

Editorial: Biomed Central

 Año de publicación: 2015

Nº de páginas: 13

Tipo de publicación: Artículo de Revista

 DOI: 10.1186/s12863-015-0267-z

ISSN: 1471-2156

Autores/as

GERVÁS ARRUGA, JAVIER

CEBOLLA, JORGE J

IRÚN, PILAR

JAVIER PEREZ LOPEZ

PLAZA, LUIS

ROCHE, JOSÉ C

CAPABLO, JOSÉ L

POCOVÍ, MIGUEL

GIRALDO, PILAR