000046921 001__ 46921
000046921 005__ 20210121114526.0
000046921 0247_ $$2doi$$a10.1186/s12863-015-0267-z
000046921 0248_ $$2sideral$$a92005
000046921 037__ $$aART-2015-92005
000046921 041__ $$aeng
000046921 100__ $$aGervas-Arruga, J.
000046921 245__ $$aIncreased glycolipid storage produced by the inheritance of a complex intronic haplotype in the aa-galactosidase A (GLA) gene
000046921 260__ $$c2015
000046921 5060_ $$aAccess copy available to the general public$$fUnrestricted
000046921 5203_ $$aBackground: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of a-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 a-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.
000046921 536__ $$9info:eu-repo/grantAgreement/ES/FIS/FIS09-02556
000046921 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000046921 590__ $$a2.152$$b2015
000046921 591__ $$aGENETICS & HEREDITY$$b100 / 166 = 0.602$$c2015$$dQ3$$eT2
000046921 592__ $$a1.176$$b2015
000046921 593__ $$aGenetics (clinical)$$c2015$$dQ2
000046921 593__ $$aGenetics$$c2015$$dQ2
000046921 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000046921 700__ $$aCebolla, J.J.
000046921 700__ $$0(orcid)0000-0003-3392-7200$$aIrun, P.
000046921 700__ $$aPerez-Lopez, J.
000046921 700__ $$aPlaza, L.
000046921 700__ $$aRoche, J.C.
000046921 700__ $$aCapablo, J.L.
000046921 700__ $$aRodriguez-Rey, J.
000046921 700__ $$0(orcid)0000-0001-8807-9187$$aPocovi, M.$$uUniversidad de Zaragoza
000046921 700__ $$0(orcid)0000-0002-8791-1901$$aGiraldo, P.
000046921 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000046921 773__ $$g16, 109 (2015), [13 pp.]$$pBMC Genet.$$tBMC GENETICS$$x1471-2156
000046921 8564_ $$s2337131$$uhttps://zaguan.unizar.es/record/46921/files/texto_completo.pdf$$yVersión publicada
000046921 8564_ $$s102074$$uhttps://zaguan.unizar.es/record/46921/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000046921 909CO $$ooai:zaguan.unizar.es:46921$$particulos$$pdriver
000046921 951__ $$a2021-01-21-11:06:38
000046921 980__ $$aARTICLE