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Fabry Disease Caused by the GLA p.Phe113Leu (p.F113L) Variant: Natural History in Males

2020Journal article Open access
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dc.contributor.authorOliveira, J
dc.contributor.authorNowak, A
dc.contributor.authorBarbey, F
dc.contributor.authorTorres, M
dc.contributor.authorNunes, J
dc.contributor.authorTeixeira-e-Costa, F
dc.contributor.authorCarvalho, F
dc.contributor.authorSampaio, S
dc.contributor.authorTavares, I
dc.contributor.authorPereira, O
dc.contributor.authorSoares, A
dc.contributor.authorCarmona, C
dc.contributor.authorCardoso, MT
dc.contributor.authorJurca-Simina, I
dc.contributor.authorSpada, M
dc.contributor.authorFerreira, S
dc.contributor.authorGermain, D
dc.date.accessioned2023-02-22T15:26:57Z
dc.date.available2023-02-22T15:26:57Z
dc.date.issued2020
dc.description.abstractBackground, aims and methods: 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. Results and conclusions: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEur J Med Genet . 2020 Feb;63(2):103703.pt_PT
dc.identifier.doi10.1016/j.ejmg.2019.103703pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/4420
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectHCC NEFpt_PT
dc.subjectAdultpt_PT
dc.subjectAgedpt_PT
dc.subjectMalept_PT
dc.subjectAllelespt_PT
dc.subjectMiddle Agedpt_PT
dc.subjectHumanspt_PT
dc.subjectCardiovascular Diseases / complicationspt_PT
dc.subjectCardiovascular Diseases / geneticspt_PT
dc.subjectCardiovascular Diseases / metabolismpt_PT
dc.subjectCerebrovascular Disorders / complicationspt_PT
dc.subjectCerebrovascular Disorders / geneticspt_PT
dc.subjectCerebrovascular Disorders / metabolismpt_PT
dc.subjectFabry Disease / complicationspt_PT
dc.subjectFabry Disease / diagnosis*pt_PT
dc.subjectFabry Disease / diagnostic imagingpt_PT
dc.subjectFabry Disease / genetics*pt_PT
dc.subjectGenotypept_PT
dc.subjectGenetic Association Studiespt_PT
dc.subjectHaplotypespt_PT
dc.subjectItaly / epidemiologypt_PT
dc.subjectMicrosatellite Repeats / geneticspt_PT
dc.subjectMutationpt_PT
dc.subjectMyocytes, Cardiac / pathologypt_PT
dc.subjectMyocytes, Cardiac / ultrastructurept_PT
dc.subjectPhenotypept_PT
dc.subjectPortugal / epidemiologypt_PT
dc.subjectRenal Insufficiency, Chronic / complicationspt_PT
dc.subjectRenal Insufficiency, Chronic / geneticspt_PT
dc.subjectRenal Insufficiency, Chronic / metabolismpt_PT
dc.subjectRisk Factorspt_PT
dc.subjectalpha-Galactosidase / genetics*pt_PT
dc.subjectalpha-Galactosidase / metabolism*pt_PT
dc.titleFabry Disease Caused by the GLA p.Phe113Leu (p.F113L) Variant: Natural History in Malespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue2pt_PT
oaire.citation.startPage103703pt_PT
oaire.citation.titleEuropean Journal of Medical Geneticspt_PT
oaire.citation.volume63pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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