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Mutation profile of FLNC gene and its prognostic relevance in patients with hypertrophic cardiomyopathy.

ABSTRACT: BACKGROUND:Filamin C (FLNC) mutation was reported as a cause of HCM, with a high probability of sudden cardiac death. However, the mutation profile of FLNC, and its relationship with phenotypic expression in HCM, remains to be elucidated. METHODS:In this study, FLNC gene was sequenced in 540 HCM patients and 307 healthy controls. RESULTS:We found that 39 (7.2%) patients carried FLNC mutations, with a similar frequency to that of controls (4.2%, p = 0.101). Pedigree analysis showed that mutations were not well segregated with HCM. The baseline characteristics between HCM patients, with and without mutations, were comparable. FLNC mutations did not increase the risk for either all-cause mortality (HR 0.746, 95% CI 0.222-2.295, p = 0.575) or cardiac mortality (HR 0.615, 95% CI 0.153-1.947, p = 0.354) in HCM patients during a follow-up of 4.7 ± 3.2 years. Moreover, there was no significant difference in survival free from sudden cardiac arrest (HR 0.721, 95% CI 0.128-3.667, p = 0.660) and heart failure (HR 0.757, 95% CI 0.318-1.642, p = 0.447). CONCLUSIONS:FLNC mutations were common in both HCM patients and healthy population. The pathogenicity of FLNC mutations detected in HCM patients and its association with the clinical outcomes should be cautiously interpreted.

SUBMITTER: Cui H

PROVIDER: S-EPMC6305649 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Mutation profile of FLNC gene and its prognostic relevance in patients with hypertrophic cardiomyopathy.

Cui Hao H Wang Jizheng J Zhang Ce C Wu Guixin G Zhu Changsheng C Tang Bing B Zou Yubao Y Huang Xiaohong X Hui Rutai R Song Lei L Wang Shuiyun S

Molecular genetics & genomic medicine 20181108 6

<h4>Background</h4>Filamin C (FLNC) mutation was reported as a cause of HCM, with a high probability of sudden cardiac death. However, the mutation profile of FLNC, and its relationship with phenotypic expression in HCM, remains to be elucidated.<h4>Methods</h4>In this study, FLNC gene was sequenced in 540 HCM patients and 307 healthy controls.<h4>Results</h4>We found that 39 (7.2%) patients carried FLNC mutations, with a similar frequency to that of controls (4.2%, p = 0.101). Pedigree analysis ...[more]

PMID: 30411535

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Project description:Background Impaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype-positive, left ventricular hypertrophy-negative). Methods and Results A single center, case-control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre-phenotypic features of HCM. Individuals with genotype-positive, left ventricular hypertrophy-negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH-fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype-positive, left ventricular hypertrophy-negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end-systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826). Conclusions Regional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

Dataset Information

Mutation profile of FLNC gene and its prognostic relevance in patients with hypertrophic cardiomyopathy.

Publications

Mutation profile of FLNC gene and its prognostic relevance in patients with hypertrophic cardiomyopathy.

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