Nawel Jaafar1, Juan Gómez2, Ikram Kammoun3, Ihsen Zairi4, Wael Ben Amara3, Salem Kachboura3, Sondes Kraiem4, Mohamed Hammami1, Sara Iglesias2, Belén Alonso2, Eliecer Coto2,5. 1. 1 Biochemistry Laboratory LR12ES05 "Nutrition-Functional Food & Vascular Health," USCR Mass Spectrometry, Faculty of Medicine, University of Monastir , Monastir, Tunisia . 2. 2 Unidad de Referencia de Cardiopatías Familiares-HUCA, Genética Molecular y Cardiología, Hospital Universitario Central Asturias , Oviedo, Spain . 3. 3 Department of Cardiology, Abderrahmen Mami Hospital , Tunis, Tunisia . 4. 4 Department of Cardiology, Habib Thameur Hospital , Tunis, Tunisia . 5. 5 Departamento de Medicina, Universidad de Oviedo , Oviedo, Spain .
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. CONCLUSION: 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.
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. CONCLUSION: 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: Gasnat Shaboodien; Timothy F Spracklen; Stephen Kamuli; Polycarp Ndibangwi; Carla Van Niekerk; Ntobeko A B Ntusi Journal: Cardiovasc Diagn Ther Date: 2020-04
Authors: Job A J Verdonschot; Els K Vanhoutte; Godelieve R F Claes; Apollonia T J M Helderman-van den Enden; Janneke G J Hoeijmakers; Debby M E I Hellebrekers; Amber de Haan; Imke Christiaans; Ronald H Lekanne Deprez; Hanne M Boen; Emeline M van Craenenbroeck; Bart L Loeys; Yvonne M Hoedemaekers; Carlo Marcelis; Marlies Kempers; Esther Brusse; Jaap I van Waning; Annette F Baas; Dennis Dooijes; Folkert W Asselbergs; Daniela Q C M Barge-Schaapveld; Pieter Koopman; Arthur van den Wijngaard; Stephane R B Heymans; Ingrid P C Krapels; Han G Brunner Journal: Hum Mutat Date: 2020-03-20 Impact factor: 4.878