FLNC pathogenic variants in patients with cardiomyopathies: Prevalence and genotype-phenotype correlations.

Autor: Ader F; APHP, UF Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Service de Biochimie Métabolique, Hôpitaux Universitaires de la Pitié- Salpêtrière- Charles Foix, Paris, France.; Sorbonne Université, UPMC Univ., INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Paris, France.; Université Paris Descartes, Faculté de Pharmacie, Paris, France., De Groote P; Pôle Cardio-Vasculaire et Pulmonaire, CHRU de Lille - Hôpital Albert Calmette, Lille, France., Réant P; Service de Cardiologie, CHU de Bordeaux, Université de Bordeaux, Paris, France., Rooryck-Thambo C; CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France., Dupin-Deguine D; Service de génétique médicale, et service d'otoneurochirurgie, CHU de Toulouse - Hôpital Purpan, Toulouse, France., Rambaud C; APHP, Service Médecine Légale, Hôpital Raymond Poincaré, Garches, France., Khraiche D; APHP, Service de Cardiologie, Hôpital Necker, Paris, France., Perret C; Sorbonne Université, UPMC Univ., INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Paris, France., Pruny JF; APHP, Centre de référence pour les maladies cardiaques héréditaires, Hôpitaux Universitaires Pitié-Salpêtrière, Paris, France., Mathieu-Dramard M; CHU Amiens Picardie, Service de Génétique Clinique, Amiens, France., Gérard M; CHU Caen, Service de Génétique Médicale, Caen, France., Troadec Y; CHU Caen, Service de Génétique Médicale, Caen, France., Gouya L; APHP, Service de Génétique Médicale, CHU Bichat-Claude Bernard, Paris, France., Jeunemaitre X; APHP, Service de génétique, Hôpital Européen Georges Pompidou, Paris, France., Van Maldergem L; Centre de génétique humaine, Université de Franche Comté, Besançon, France., Hagège A; APHP, Service de Cardiologie, Hôpital Européen Georges Pompidou, Paris, France., Villard E; Sorbonne Université, UPMC Univ., INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Paris, France., Charron P; Sorbonne Université, UPMC Univ., INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Paris, France.; APHP, Centre de référence pour les maladies cardiaques héréditaires, Hôpitaux Universitaires Pitié-Salpêtrière, Paris, France., Richard P; APHP, UF Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Service de Biochimie Métabolique, Hôpitaux Universitaires de la Pitié- Salpêtrière- Charles Foix, Paris, France.; Sorbonne Université, UPMC Univ., INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Paris, France.; APHP, Centre de référence pour les maladies cardiaques héréditaires, Hôpitaux Universitaires Pitié-Salpêtrière, Paris, France.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2019 Oct; Vol. 96 (4), pp. 317-329. Date of Electronic Publication: 2019 Jul 18.
DOI: 10.1111/cge.13594
Abstrakt: Pathogenic variants in FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes. Our aim was to estimate the prevalence of FLNC pathogenic variants in subtypes of cardiomyopathies and to study the relations between phenotype and genotype. DNAs from a cohort of 1150 unrelated index-patients with isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 51 cardiomyopathy disease-causing genes. An FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1% to 8% depending on the cardiomyopathy subtype. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame indel variants were found in other phenotypes. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (P = .01). This work reported the first observation of a left ventricular non-compaction associated with a unique probably causal variant in FLNC which highlights the role of FLNC in cardiomyopathies. A correlation between the nature of the variant and the cardiomyopathy subtype was observed as well as with SCD risk.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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