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Hypertrophic cardiomyopathy in a Portuguese population: mutations in the myosin-binding protein C gene

Item Type:Article
Title:Hypertrophic cardiomyopathy in a Portuguese population: mutations in the myosin-binding protein C gene
Creators Name:Cardim, N. and Perrot, A. and Santos, S. and Morgado, P. and Padua, M. and Ferreira, S. and Reis, R.P. and Monteiro, C. and Ferreira, T. and Correia, J.M. and Osterziel, K.J.
Abstract:BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease and is often a consequence of mutations in the myosin-binding protein C gene (MYBPC3). Until now, however, no systematic review has been published on mutations of this gene in a Portuguese population. OBJECTIVES: In a Portuguese population of HCM patients: 1) to determine the prevalence of mutations in the MYBPC3 gene; 2) to characterize the mutations genetically; 3) to analyze the phenotype and compare it with the genotype-phenotype correlations for mutations in this gene described in the literature. METHODS: We studied 45 consecutive index patients with HCM (41 with familial HCM). In each patient, we performed a genetic study to detect mutations in the MYBPC3 gene. Once a mutation was identified and genetically characterized, a broad phenotypic evaluation was performed. The genetic and clinical data were then compared with those described in the literature. RESULTS: Of the 45 patients, 5 (11.1%) showed mutations in the MYBPC3 gene (2 deletions and 3 missense mutations), all in patients with familial HCM. Of these, 4 were 'new' mutations: Ala 522 Thr (exon 17); Gli 1205 Asp (exon 32); Lis 505 Del (exon 17) and Lis 813 Del (exon 25). The other mutation, Arg 502 Gln (exon 17), had been previously described in the literature. Three of the 5 mutations were located in exon 17. Four of these 5 patients were symptomatic, mainly with heart failure and supraventricular arrhythmias. No patient was at high risk for sudden cardiac death. Most of the patients had non-obstructive HCM. The ECG, echocardiogram, Holter monitoring and treadmill exercise test showed highly variable results, reflecting the heterogeneity typical of this disease. CONCLUSIONS: In a Portuguese population of 45 HCM patients, 5 (11.1%) had mutations in the MYBPC3 gene (3 missense mutations--theoretically less frequent in the MYBPC3 gene--and 2 deletions). Four of these were 'new' mutations and 3 of them were located in exon 17 (which may be a 'hot spot' for MYBPC3 gene mutations in the Portuguese population). In all the patients, the phenotypic expression was different from that usually described for these mutations; in 3 of our patients, the clinical manifestations and penetrance were of early onset and one patient had a highly symptomatic form of obstructive hypertrophic cardiomyopathy. These data reflect the large number of exceptions to the classic genotype-phenotype correlations in HCM, highlighting the role of other factors, genetic and non-genetic, in regulating penetrance, clinical expression and prognosis in each family and in each individual patient.
Keywords:Hypertrophic Cardiomyopathy, Carrier Proteins
Source:Revista Portuguesa de Cardiologia
Publisher:Sociedade Portuguesa de Cardiologia
Page Range:1463-1476
Date:December 2005
PubMed:View item in PubMed

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