Identification of a Novel <i>GLA</i> Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype
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- Csányi Beáta
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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- Hategan Lidia
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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- Nagy Viktória
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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- Obál Izabella
- Department of Neurology, University of Szeged
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- Varga Edina T.
- Department of Neurology, University of Szeged
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- Borbás János
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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- Tringer Annamária
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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- Eichler Sabrina
- Centogene AG
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- Forster Tamás
- Centogene AG
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- Rolfs Arndt
- Centogene AG Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock
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- Sepp Róbert
- 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged
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説明
<p>Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.</p>
収録刊行物
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- International Heart Journal
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International Heart Journal 58 (3), 454-458, 2017
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