Abstract | BACKGROUND: 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.
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Authors | Nuno Cardim, Andreas Perrot, Susana Santos, Paulo Morgado, Mário Pádua, Sara Ferreira, R Palma Reis, Carolino Monteiro, Teresa Ferreira, J Martins Correia, Karol J Osterziel |
Journal | Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology
(Rev Port Cardiol)
Vol. 24
Issue 12
Pg. 1463-76
(Dec 2005)
ISSN: 0870-2551 [Print] Portugal |
PMID | 16566405
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- myosin-binding protein C
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Cardiomyopathy, Hypertrophic
(genetics)
- Carrier Proteins
(genetics)
- Female
- Humans
- Male
- Middle Aged
- Mutation
- Phenotype
- Portugal
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