View : 22 Download: 0

Fabry disease: Biochemical, pathological and structural studies of the α-galactosidase A with E66Q amino acid substitution

Title
Fabry disease: Biochemical, pathological and structural studies of the α-galactosidase A with E66Q amino acid substitution
Authors
Togawa T.Tsukimura T.Kodama T.Tanaka T.Kawashima I.Saito S.Ohno K.Fukushige T.Kanekura T.Satomura A.Kang D.-H.Lee B.H.Yoo H.-W.Doi K.Noiri E.Sakuraba H.
Ewha Authors
강덕희
SCOPUS Author ID
강덕희scopus
Issue Date
2012
Journal Title
Molecular Genetics and Metabolism
ISSN
1096-7192JCR Link
Citation
vol. 105, no. 4, pp. 615 - 620
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Recently, male subjects harboring the c.196G. >. C nucleotide change which leads to the E66Q enzyme having low α-galactosidase A (GLA) activity have been identified at an unexpectedly high frequency on Japanese and Korean screening for Fabry disease involving dry blood spots and plasma/serum samples. Individuals with the E66Q enzyme have been suspected to have the later-onset Fabry disease phenotype leading to renal and cardiac disease. However, there has been no convincing evidence for this. To determine whether c.196G. >. C (E66Q) is disease-causing or not, we performed biochemical, pathological and structural studies. It was predicted that the E66Q amino acid substitution causes a small conformational change on the molecular surface of GLA, which leads to instability of the enzyme protein. However, biochemical studies revealed that subjects harboring the E66Q enzyme exhibited relatively high residual enzyme activity in white blood cells, and that there was no accumulation of globotriaosylceramide in cultured fibroblasts or an increased level of plasma globotriaosylsphingosine in these subjects. An electron microscopic examination did not reveal any pathological changes specific to Fabry disease in biopsied skin tissues from a male subject with the E66Q enzyme. These results strongly suggest that the c.196G. >. C is not a pathogenic mutation but is a functional polymorphism. © 2012 Elsevier Inc..
DOI
10.1016/j.ymgme.2012.01.010
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE