Novel filamin C (FLNC) variant causes a severe form of familial mixed hypertrophic-restrictive cardiomyopathy.
atriomyopathy
familial
filamin C
hypertrophic cardiomyopathy
restrictive cardiomyopathy
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
12
12
2022
received:
11
07
2022
accepted:
10
02
2023
medline:
11
5
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Variants of filamin C (FLNC) have been identified as rare genetic substrate for hypertrophic cardiomyopathy (HCM). Data on the clinical course of FLNC-related HCM are conflicting with some studies suggesting mild phenotypes whereas other studies have reported more severe outcomes. In this study, we present a novel FLNC variant (Ile1937Asn) that was identified in a large family of French-Canadian descent with excellent segregation data. FLNC-Ile1937Asn is a novel missense variant characterized by full penetrance and poor clinical outcomes. End stage heart failure requiring transplantation occurred in 43% and sudden cardiac death in 29% of affected family members. Other particular features of FLNC-Ile1937Asn include an early disease onset (mean age of 19 years) and the development of a marked atrial myopathy (severe biatrial dilatation with remodeling and multiple complex atrial arrhythmias) that was present in all gene carriers. The FLNC-Ile1937Asn variant is a novel, pathogenic mutation resulting in a severe form of HCM with full disease penetrance. The variant is associated with a high proportion of end-stage heart failure, heart transplantation, and disease-related mortality. Close follow-up and appropriate risk stratification of affected individuals at specialized heart centers is recommended.
Identifiants
pubmed: 36864778
doi: 10.1002/ajmg.a.63169
doi:
Substances chimiques
Filamins
0
FLNC protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1508-1517Informations de copyright
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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