title: Genetic basis of end-stage hypertrophic cardiomyopathy.
abstract: OBJECTIVE
  Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous presentation and clinical course. A minority of HCM patients develop end-stage HCM and require cardiac transplantation. The genetic basis of end-stage HCM is unknown but small series, isolated case reports and animal models have related the most aggressive heart failure course with the presence of multiple mutations.
  
  
  RESULTS
  Twenty-six patients (age 40.4 ± 14.5 years; 46% male) transplanted for end-stage HCM underwent genetic screening of 10 HCM-related genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, TNNC1, MYL3, MYL2, ACTC, LDB3). Additional genetic screening of LAMP2/PRKAG2 and mitochondrial DNA (mtDNA) was performed in four and three cases, respectively. Findings were correlated with clinical and histological features. Pathogenic mutations were identified in 15 patients (58%). Thirteen patients (50%) had mutations in sarcomeric genes (six in MYH7, three in MYBPC3, two in MYL2, one in TNNI3, and one in MYL3) and two patients had mutations in LAMP2. Only three patients (13%) had double mutations and all in homozygosis. Except for a more frequent family history of HCM, patients with mutations in sarcomeric genes did not show any clinical feature that distinguished them from patients without mutations in these genes. Evaluation of 44 relatives from 12 families identified 13 mutation carriers, 9 of whom had an overt HCM phenotype.
  
  
  CONCLUSIONS
  Heart transplanted HCM has a heterogeneous genetic background where multiple mutations are uncommon. The clinical course of HCM is not primarily dependent on the presence of multiple sarcomeric mutations. Clinical and genetic evaluation of relatives does not support differential clinical management in HCM based on genetics.
authors: Cardiomyopathy Unit, Heart Transplant Program, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain. pablogpavia@yahoo.es
authors: Pablo
authors: P
authors: Garcia-Pavia
authors: Maria E
authors: ME
authors: Vázquez
authors: Javier
authors: J
authors: Segovia
authors: Clara
authors: C
authors: Salas
authors: Patricia
authors: P
authors: Avellana
authors: Manuel
authors: M
authors: Gómez-Bueno
authors: Carlos
authors: C
authors: Vilches
authors: M Esther
authors: ME
authors: Gallardo
authors: Rafael
authors: R
authors: Garesse
authors: Jesús
authors: J
authors: Molano
authors: Belén
authors: B
authors: Bornstein
authors: Luis
authors: L
authors: Alonso-Pulpon
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005838:Genotype; D016027:Heart Transplantation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence