ArticleMolecular genetics and metabolism2015
The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.
Article in Molecular genetics and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations.International journal of molecular sciences · 2016Pooled it
- Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing.Scientific reports · 2021Trial
- Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry.Journal of medical genetics · 2016Trial
- Screening for Fabry Disease Among Dialysis Patients: A Multicenter Cross-Sectional Study in Türkiye with Cascade Screening of Identified Cases.Medicina (Kaunas, Lithuania) · 2026Article
- Clinical and Biochemical Characterization of Fabry Disease Associated GLA Gene Variants: Data From a Large Cohort of 469 Thousand Genotyped Subjects of the UK Biobank Database.Journal of inherited metabolic disease · 2025Article
- Correlation of enzyme activities and genotype with clinical manifestations in Chinese patients of different sexes with classical and late-onset Fabry disease.Frontiers of medicine · 2025Article
- Exome sequencing of a Portuguese cohort of early-onset Alzheimer's disease implicates the X-linked lysosomal gene GLA.Scientific reports · 2025Article
- Screening for Fabry Disease-Related Mutations Among 829 Kidney Transplant Recipients.Journal of clinical medicine · 2024Article
- Establishing Treatment Effectiveness in Fabry Disease: Observation-Based Recommendations for Improvement.International journal of molecular sciences · 2024Review
- Cases of Fabry Disease in Which Pathogenic Variants Are Not Detected in Parent-Child Pairs.Cureus · 2024Article
- Difficulties in Diagnosing Fabry Disease in Patients with Unexplained Left Ventricular Hypertrophy (LVH): Is the Novel GLA Gene Mutation a Pathogenic Mutation or Polymorphism?Balkan journal of medical genetics : BJMG · 2023Article
- The evolution of the initial manifestations and renal involvement of chinese patients with classical and late-onset Fabry disease at different sexes and ages.BMC nephrology · 2023Article
- Phenotyping of a novelFrontiers in genetics · 2023Article
- Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment.Journal of personalized medicine · 2022Article
- Challenging the traditional approach for interpreting genetic variants: Lessons from Fabry disease.Clinical genetics · 2022Review
- Clinical Characteristics, Renal Involvement, and Therapeutic Options of Pediatric Patients With Fabry Disease.Frontiers in pediatrics · 2022Review
- High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review.Diagnostics (Basel, Switzerland) · 2021Review
- Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic.Journal of clinical medicine · 2021Article
- The benefits and challenges of family genetic testing in rare genetic diseases-lessons from Fabry disease.Molecular genetics & genomic medicine · 2021Review
- Oxidative stress biomarkers in Fabry disease: is there a room for them?Journal of neurology · 2020Article
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Authors and funding
21 authors at 16 institutions in 4 countries.
Funding
Abstract
Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.
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