Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males.

Details

Serval ID
serval:BIB_8A051DBE6C82
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males.
Journal
European journal of medical genetics
Author(s)
Oliveira J.P., Nowak A., Barbey F., Torres M., Nunes J.P., Teixeira-E-Costa F., Carvalho F., Sampaio S., Tavares I., Pereira O., Soares A.L., Carmona C., Cardoso M.T., Jurca-Simina I.E., Spada M., Ferreira S., Germain D.P.
ISSN
1878-0849 (Electronic)
ISSN-L
1769-7212
Publication state
Published
Issued date
02/2020
Peer-reviewed
Oui
Volume
63
Number
2
Pages
103703
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The α-galactosidase gene (GLA) c.337T>C/p.Phe113Leu variant was originally described in patients with late-onset cardiac forms of Fabry disease (FD), who had residual α-galactosidase activity. It has since emerged as the most commonly reported GLA variant in Portuguese subjects diagnosed with FD but is also prevalent in the Italian population, where two boys carrying the GLA Leu113 allele were identified in a large-scale newborn screening program, the variant allele segregating in both cases with the same surrounding haplotype. To further delineate the genotype-phenotype correlations of this GLA variant, we have reviewed the natural history and clinical phenotypes of 11 symptomatic Portuguese males, from 10 unrelated families originating from several different areas in mainland Portugal and Madeira Island, who were diagnosed with FD associated with the GLA Leu113 allele in a diversity of clinical and screening settings. Nine of the patients were the probands of their respective families. To test whether the GLA Leu113 allele inherited by the 10 Portuguese and the two Italian families resulted from independent mutational events, we have additionally performed a haplotype analysis with 5 highly polymorphic, closely linked microsatellite markers surrounding the GLA gene.
Hemizygosity for the GLA Leu113 variant allele is associated with a late-onset form of FD, invariably presenting with severe cardiac involvement. Clinically relevant cerebrovascular and kidney involvement may also occur in some patients but the pathogenic relationship between the incomplete α-galactosidase deficiency and the risks of stroke and of chronic kidney disease is not straightforward. The observation that the Leu113 allele segregated within the same GLA microsatellite haplotype in both the Portuguese and Italian families suggests its inheritance from a common ancestor.
Keywords
Alpha-galactosidase gene (GLA), Fabry disease, Haplotype, Microsatellite markers, p.Phe113Leu (p.F113L) pathogenic variant
Pubmed
Create date
30/06/2019 16:09
Last modification date
18/02/2020 7:20
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