Article

A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy.

CEINGE-Biotecnologie Avanzate s.c.ar.l., Naples, Italy.
Clinical Genetics (impact factor: 3.13). 08/2009; 76(1):91-101. DOI:10.1111/j.1399-0004.2009.01190.x pp.91-101
Source: PubMed

ABSTRACT Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disorder worldwide. It is the leading cause of sudden cardiac-related death in young people and a major cause of cardiac failure and death in elderly people. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information that could be useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 families with HCM from southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these individuals had no signs or symptoms suggestive of HCM. This study, besides characterizing the spectrum of mutations in another childhood population, and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype-phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures.

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    E Blair, C Redwood, H Ashrafian, M Oliveira, J Broxholme, B Kerr, A Salmon, I Ostman-Smith, H Watkins
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Keywords

12 mutations
 
asymptomatic candidates
 
cardiac failure
 
childhood population
 
families
 
family members available
 
frequent genetic cardiovascular disorder
 
greater genetic heterogeneity
 
increase genotype-phenotype correlations
 
major cause
 
mutations
 
myofilament gene mutations
 
overt signs
 
remaining 23 families
 
silent HCM
 
southern Italy
 
sudden cardiac-related death
 
symptoms suggestive
 
therapeutic measures
 
young people