A mutation update for the FLNC gene in myopathies and cardiomyopathies.
FLNC
cardiomyopathy
filamin
genotype-phenotype correlation
myopathy
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
20
12
2019
revised:
12
02
2020
accepted:
25
02
2020
pubmed:
1
3
2020
medline:
6
11
2021
entrez:
1
3
2020
Statut:
ppublish
Résumé
Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype-phenotype correlations based on available evidence.
Identifiants
pubmed: 32112656
doi: 10.1002/humu.24004
pmc: PMC7318287
doi:
Substances chimiques
FLNC protein, human
0
Filamins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1091-1111Informations de copyright
© 2020 The Authors. Human Mutation published by Wiley Periodicals, Inc.
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