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Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns

Title
Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns
Authors
Lee B.H.Heo S.H.Kim G.-H.Park J.-Y.Kim W.-S.Kang D.-H.Choe K.H.Kim W.-H.Yang S.H.Yoo H.-W.
Ewha Authors
강덕희
SCOPUS Author ID
강덕희scopus
Issue Date
2010
Journal Title
Journal of Human Genetics
ISSN
1434-5161JCR Link
Citation
vol. 55, no. 8, pp. 512 - 517
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Fabry disease is caused by an α-galactosidase A (GLA) deficiency. In this study, we identified 28 unrelated Korean families with Fabry disease with 25 distinct mutations in the GLA gene including six novel mutations (p.W47X, p.C90X, p.D61EfsX32, IVS4 11 TA, p.D322E and p.W349). Notably, five subjects from four unrelated families carried the p.E66Q variant, previously known as a pathogenic mutation in atypical Fabry disease. Among these patients, only one had proteinuria and two had hypertrophic cardiomyopathy without any other systemic manifestation of Fabry disease. Substantial residual GLA activity was shown both in the leukocytes of p.E66Q patients (19.0-30.3% of normal activity) and in transiently overexpressed COS-7 cells (43.83.03% of normal activity). Although GLA harboring p.E66Q is unstable at neutral pH, the enzyme is efficiently expressed in the lysosomes of COS-7 cells. The location of p.E66 is distant from both the active site and the dimer interface, and has a more accessible surface area than have other mutations of atypical Fabry disease. In addition, the allele frequency of p.E66Q determined in 833 unrelated Korean individuals was remarkably high at 1.046% (95% confidence interval, 0.458-1.634%). These results indicate that p.E66Q is a functional polymorphism rather than a pathogenic mutation. © 2010 The Japan Society of Human Genetics. All rights reserved.
DOI
10.1038/jhg.2010.58
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의학전문대학원 > 의학과 > Journal papers
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