title: Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) in infants and children is thought to be commonly associated with metabolic disorders and malformation syndromes. Familial disease caused by mutations in cardiac sarcomere protein genes, which accounts for most cases in adolescents and adults, is believed to be a very rare cause of HCM.
  
  
  RESULTS
  Seventy-nine consecutive patients diagnosed with HCM aged 13 years or younger underwent detailed clinical and genetic evaluation. The protein-coding sequences of 9 sarcomere protein genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, ACTC, and TNNC1), the genes encoding desmin (DES), and the gamma-2 subunit of AMP kinase (PRKAG2) were screened for mutations. A family history of HCM was present in 48 patients (60.8%). Forty-seven mutations (15 novel) were identified in 42 (53.2%) patients (5 patients had 2 mutations). The genes most commonly implicated were MYH7 (48.9%) and MYBPC3 (36.2%); mutations in TNNT2, ACTC, MYL3, and TNNI3 accounted for <5% of cases each. A total of 16.7% patients with sarcomeric mutations were diagnosed before 1 year of age. There were no differences in clinical and echocardiographic features between those children with sarcomere protein gene mutations and those without or between patients with 2 mutations and those with 1 or no mutations.
  
  
  CONCLUSIONS
  This study shows that familial disease is common among infants and children with HCM and that, in most cases, disease is caused by mutations in cardiac sarcomere protein genes. The major implication is that all first-degree relatives of any child diagnosed with HCM should be offered screening. Furthermore, the finding that one sixth of patients with sarcomeric disease were diagnosed in infancy suggests that current views on pathogenesis and natural history of familial HCM may have to be revised.
authors.affiliation: Inherited Cardiovascular Diseases Unit, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Kaski
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Maria Teresa Tome
authors.initials: MT
authors.lastname: Esteban
authors.forename: Sharon
authors.initials: S
authors.lastname: Jenkins
authors.forename: Antonios
authors.initials: A
authors.lastname: Pantazis
authors.forename: John E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007087:Illinois / Q000453:epidemiology; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D012518:Sarcomeres / Q000235:genetics* / Q000378:metabolism / Q000473:pathology