GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease?
| Autor: | Ândrea Virgínia Chaves-Markman, Ricardo Flores Pires, Andréa Bezerra de Melo da Silveira Lordsleem, Eveline Barros Calado, Brivaldo Markman Filho, Dinaldo Cavalcanti de Oliveira, Catarina Maria Fonseca Pereira, Sandro Gonçalves de Lima, Marcelo Antônio Oliveira Santos-Veloso, Manuel Markman |
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| Jazyk: | angličtina |
| Předmět: |
lcsh:Diseases of the circulatory (Cardiovascular) system
Alpha-galactosidase biology Fabry Disease/genetic business.industry Hypertrophic cardiomyopathy 030204 cardiovascular system & hematology New variant Cardiomyopathy Hypertrophic medicine.disease Fabry's disease Molecular biology Fabry disease Glycosphingolipids 03 medical and health sciences 0302 clinical medicine Gla gene lcsh:RC666-701 biology.protein Medicine lipids (amino acids peptides and proteins) Hypertrophy Left Ventricular cardiovascular diseases Cardiology and Cardiovascular Medicine business |
| Zdroj: | Arquivos Brasileiros de Cardiologia, Vol 113, Iss 1, Pp 77-84 Arquivos Brasileiros de Cardiologia v.113 n.1 2019 Arquivos Brasileiros de Cardiologia Sociedade Brasileira de Cardiologia (SBC) instacron:SBC |
| ISSN: | 1678-4170 |
| Popis: | Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), causing multiple organ dysfunctions. Objective: To perform GLA gene screening in a group of patients with echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM). Methods: a cross-sectional study was conducted with HCM patients from a university hospital. Patients with coronary artery disease and valvulopathies were excluded. Mutation analysis of the GLA gene was performed. In male subjects, the analysis was performed after evidence of low α-Gal A activity. Results: 60 patients with echocardiographic diagnosis of HCM were included. Age ranged from 12 to 85 years and 60% were women. Mean myocardial fibrosis percentage on MRI was 10.7 ± 13.1% and mean ventricular thickness was18.7 ± 6.7 mm. Four patients had the following GLA gene mutations: c.967C>A (p.Pro323Thr), not yet described in the literature; c.937G>T (p.Asp313Tyr); and c.352C>T (p.Arg118Cys). All patients had normal levels of lyso-Gb3 and non-ischemic myocardial fibrosis on magnetic resonance imaging; one patient had proteinuria and one patient had ventricular tachycardia. Conclusion: in this study, the frequency of mutation in the GLA gene in patients with HCM was 6.7%. A novel mutation in exon 6 of the GLA gene, c.967C>A (p.Pro323Thr), was identified. Patients with HCM may have GLA mutations and FD should be ruled out. Plasma (lyso-Gb3) levels do not seem to be sufficient to attain a diagnosis and organ biopsy should be considered. |
| Databáze: | OpenAIRE |
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