Your browser doesn't support javascript.
loading
Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies.
Mazzarotto, Francesco; Hawley, Megan H; Beltrami, Matteo; Beekman, Leander; de Marvao, Antonio; McGurk, Kathryn A; Statton, Ben; Boschi, Beatrice; Girolami, Francesca; Roberts, Angharad M; Lodder, Elisabeth M; Allouba, Mona; Romeih, Soha; Aguib, Yasmine; Baksi, A John; Pantazis, Antonis; Prasad, Sanjay K; Cerbai, Elisabetta; Yacoub, Magdi H; O'Regan, Declan P; Cook, Stuart A; Ware, James S; Funke, Birgit; Olivotto, Iacopo; Bezzina, Connie R; Barton, Paul J R; Walsh, Roddy.
Afiliación
  • Mazzarotto F; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
  • Hawley MH; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  • Beltrami M; National Heart and Lung Institute, Imperial College London, London, UK.
  • Beekman L; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • de Marvao A; Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
  • McGurk KA; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
  • Statton B; Amsterdam UMC, University of Amsterdam, Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam, Netherlands.
  • Boschi B; MRC London Institute of Medical Sciences, Imperial College London, London, UK.
  • Girolami F; National Heart and Lung Institute, Imperial College London, London, UK.
  • Roberts AM; MRC London Institute of Medical Sciences, Imperial College London, London, UK.
  • Lodder EM; Genetic Unit, Careggi University Hospital, Florence, Italy.
  • Allouba M; Department of Paediatric Cardiology, Meyer Children's Hospital, Florence, Italy.
  • Romeih S; National Heart and Lung Institute, Imperial College London, London, UK.
  • Aguib Y; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Baksi AJ; Amsterdam UMC, University of Amsterdam, Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam, Netherlands.
  • Pantazis A; Aswan Heart Centre, Aswan, Egypt.
  • Prasad SK; Aswan Heart Centre, Aswan, Egypt.
  • Cerbai E; Aswan Heart Centre, Aswan, Egypt.
  • Yacoub MH; National Heart and Lung Institute, Imperial College London, London, UK.
  • O'Regan DP; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Cook SA; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Ware JS; National Heart and Lung Institute, Imperial College London, London, UK.
  • Funke B; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Olivotto I; Department of Neurosciences, Psychology, Drug Research and Child Health (NeuroFarBa), University of Florence, Florence, Italy.
  • Bezzina CR; Aswan Heart Centre, Aswan, Egypt.
  • Barton PJR; National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, London, UK.
  • Walsh R; MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Genet Med ; 23(5): 856-864, 2021 05.
Article en En | MEDLINE | ID: mdl-33500567
PURPOSE: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. METHODS: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). RESULTS: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. CONCLUSION: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Cardiomiopatía Dilatada / Cardiopatías Congénitas / Cardiomiopatías Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Cardiomiopatía Dilatada / Cardiopatías Congénitas / Cardiomiopatías Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Italia