title: Spectrum of Mutations in Hypertrophic Cardiomyopathy Genes Among Tunisian Patients.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder associated with heart failure and sudden death. Mutations in the cardiac sarcomere genes are found in approximately half of HCM patients and are more common among cases with a family history of the disease. Data about the mutational spectrum of the sarcomeric genes in HCM patients from Northern Africa are limited. The population of Tunisia is particularly interesting due to its Berber genetic background. As founder mutations have been reported in other disorders.
  
  
  METHODS
  We performed semiconductor chip (Ion Torrent PGM) next generation sequencing of the nine main sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, ACTC1, TNNC1, MYL2, MYL3, TPM1) as well as the recently identified as an HCM gene, FLNC, in 45 Tunisian HCM patients.
  
  
  RESULTS
  We found sarcomere gene polymorphisms in 12 patients (27%), with MYBPC3 and MYH7 representing 83% (10/12) of the mutations. One patient was homozygous for a new MYL3 mutation and two were double MYBPC3 + MYH7 mutation carriers. Screening of the FLNC gene identified three new mutations, which points to FLNC mutations as an important cause of HCM among Tunisians.
  
  
  CONCLUSIONS
  The mutational background of HCM in Tunisia is heterogeneous. Unlike other Mendelian disorders, there were no highly prevalent mutations that could explain most of the cases. Our study also suggested that FLNC mutations may play a role on the risk for HCM among Tunisians.
authors: 1 Biochemistry Laboratory LR12ES05 "Nutrition-Functional Food & Vascular Health," USCR Mass Spectrometry, Faculty of Medicine, University of Monastir , Monastir, Tunisia .
authors: Nawel
authors: N
authors: Jaafar
authors: 2 Unidad de Referencia de Cardiopatías Familiares-HUCA, Genética Molecular y Cardiología, Hospital Universitario Central Asturias , Oviedo, Spain .
authors: Juan
authors: J
authors: Gómez
authors: 3 Department of Cardiology, Abderrahmen Mami Hospital , Tunis, Tunisia .
authors: Ikram
authors: I
authors: Kammoun
authors: 4 Department of Cardiology, Habib Thameur Hospital , Tunis, Tunisia .
authors: Ihsen
authors: I
authors: Zairi
authors: 3 Department of Cardiology, Abderrahmen Mami Hospital , Tunis, Tunisia .
authors: Wael Ben
authors: WB
authors: Amara
authors: 3 Department of Cardiology, Abderrahmen Mami Hospital , Tunis, Tunisia .
authors: Salem
authors: S
authors: Kachboura
authors: 4 Department of Cardiology, Habib Thameur Hospital , Tunis, Tunisia .
authors: Sondes
authors: S
authors: Kraiem
authors: 1 Biochemistry Laboratory LR12ES05 "Nutrition-Functional Food & Vascular Health," USCR Mass Spectrometry, Faculty of Medicine, University of Monastir , Monastir, Tunisia .
authors: Mohamed
authors: M
authors: Hammami
authors: 2 Unidad de Referencia de Cardiopatías Familiares-HUCA, Genética Molecular y Cardiología, Hospital Universitario Central Asturias , Oviedo, Spain .
authors: Sara
authors: S
authors: Iglesias
authors: 2 Unidad de Referencia de Cardiopatías Familiares-HUCA, Genética Molecular y Cardiología, Hospital Universitario Central Asturias , Oviedo, Spain .
authors: Belén
authors: B
authors: Alonso
authors: 2 Unidad de Referencia de Cardiopatías Familiares-HUCA, Genética Molecular y Cardiología, Hospital Universitario Central Asturias , Oviedo, Spain .|5 Departamento de Medicina, Universidad de Oviedo , Oviedo, Spain .
authors: Eliecer
authors: E
authors: Coto
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics* / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D064448:Filamins / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D015995:Prevalence; D012518:Sarcomeres / Q000235:genetics; D014416:Tunisia; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D064448:Filamins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human
keywords: filamin C; genetic testing; hypertrophic cardiomyopathy; next generation sequencing; sarcomere genes