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

BMC Genetics
Javier Gervas-ArrugaPilar Giraldo

Abstract

Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-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 α-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. 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 ...Continue Reading

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Citations

Jun 25, 2017·European Journal of Pediatrics·Cristobal ColonJosé R Fernández-Lorenzo
Mar 16, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hiroki MaruyamaSatoshi Ishii
Apr 11, 2018·Orphanet Journal of Rare Diseases·Irene VieitezSaida Ortolano
Dec 12, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Raphael SchiffmannXiaoyang Wu
Jun 14, 2021·Pediatric Rheumatology Online Journal·Luciana Paim-MarquesSimone Appenzeller

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Methods Mentioned

BETA
Assay
PCR
electrophoresis
Infrared Imaging
light microscopy
biopsies
confocal microscopy

Software Mentioned

SSPNN
Genomatix
FV10
ASW
VibraCell
MatInspector
SPSS
Olympus

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