BibTex format
@article{de:2026:10.1016/j.hrthm.2026.01.054,
author = {de, Villiers C and Ormondroyd, E and Thomson, K and Ormerod, JOM and Sarwar, R and Waring, A and Bagnall, RD and Sparrow, A and Steeples, V and Blair, E and Buchan, RJ and Bueno-Orovio, A and Dent, T and Farrall, M and Harper, AR and Hastings, R and Jones, S and Krishnan, N and Lise, S and Pagnamenta, AT and Salatino, S and Seed, L and Taylor, JC and Weintraub, RG and West, D and WGS500, Consortium and Ware, JS and Ingles, J and Semsarian, C and Watkins, H},
doi = {10.1016/j.hrthm.2026.01.054},
journal = {Heart Rhythm},
title = {Hypertrophic cardiomyopathy caused by Filamin-C (FLNC) variants has restrictive and extracardiac features and a distinctive ECG.},
url = {http://dx.doi.org/10.1016/j.hrthm.2026.01.054},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Filamin-C (FLNC) gene variants are associated with cardiac and skeletal muscle diseases including a clear role of loss-of-function variants in dilated cardiomyopathy. OBJECTIVE: To assess the contribution of rare FLNC variants to hypertrophic/restrictive cardiomyopathy (HCM/RCM). METHODS: Family-based studies in two specialist services, and statistical modelling of rare FLNC missense variants, using a cohort of 3,289 sarcomere-negative HCM cases and 122,348 genome aggregation database controls. RESULTS: Clinical evaluation of patients with HCM/RCM and a rare FLNC variant identified a distinct ECG repolarisation phenotype in 37% (19/51 individuals, from 12 families) which was observed in only 1.0% (2/197) of a control HCM cohort. FLNC variant carriers with the characteristic ECG had smaller LV cavity size, lower contractility, more severe diastolic dysfunction, and were more likely to have a restrictive phenotype. Heart failure death, transplant or cardiac arrest occurred in at least one individual in seven of the 12 families (58%) in the 'ECG positive' group, and musculoskeletal abnormalities were present in four families (33%). Five of 12 variants (41.7%) in the 'ECG positive' group co-segregated, and two were apparently de novo. Eleven variants were missense, one splice site. Rare FLNC missense variant burden indicated a low case excess amongst all HCM cases (etiological fraction 0.45, 95% CI [0.36-0.54]), but in 'ECG positive' cases the etiological fraction was substantially higher (0.98, 95% CI [0.97-0.99]). CONCLUSION: Pathogenic FLNC variants in patients with HCM/RCM are non-truncating and cause a discrete phenotype comprising a characteristic ECG, hypertrophic and restrictive features without hypercontractility, and extra-cardiac abnormalities.
AU - de,Villiers C
AU - Ormondroyd,E
AU - Thomson,K
AU - Ormerod,JOM
AU - Sarwar,R
AU - Waring,A
AU - Bagnall,RD
AU - Sparrow,A
AU - Steeples,V
AU - Blair,E
AU - Buchan,RJ
AU - Bueno-Orovio,A
AU - Dent,T
AU - Farrall,M
AU - Harper,AR
AU - Hastings,R
AU - Jones,S
AU - Krishnan,N
AU - Lise,S
AU - Pagnamenta,AT
AU - Salatino,S
AU - Seed,L
AU - Taylor,JC
AU - Weintraub,RG
AU - West,D
AU - WGS500,Consortium
AU - Ware,JS
AU - Ingles,J
AU - Semsarian,C
AU - Watkins,H
DO - 10.1016/j.hrthm.2026.01.054
PY - 2026///
TI - Hypertrophic cardiomyopathy caused by Filamin-C (FLNC) variants has restrictive and extracardiac features and a distinctive ECG.
T2 - Heart Rhythm
UR - http://dx.doi.org/10.1016/j.hrthm.2026.01.054
UR - https://www.ncbi.nlm.nih.gov/pubmed/41672210
ER -