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

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Item Type:	Article
Title:	Hypertrophic cardiomyopathy in a Portuguese population: mutations in the myosin-binding protein C gene
Creators Name:	Cardim, N., Perrot, A., Santos, S., Morgado, P., Padua, M., Ferreira, S., Reis, R.P., Monteiro, C., Ferreira, T., 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
ISSN:	0870-2551
Publisher:	Sociedade Portuguesa de Cardiologia
Volume:	24
Number:	12
Page Range:	1463-1476
Date:	December 2005
PubMed:	View item in PubMed

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