Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation
Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation
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DOI：
10.1093/eurheartj/ehx596
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发表时间：
2018-03-07
影响因子：
39.3
通讯作者：
Haugaa, Kristina Hermann
中科院分区：
文献类型：
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作者：
Hasselberg, Nina Eide;Haland, Trine Fink;Haugaa, Kristina Hermann
目的核纤层蛋白A/C（LMNA）基因突变导致家族性扩张型心肌病（DCM），并伴有频繁的传导阻滞和心律失常。我们探讨了挪威家族性DCM中LMNA突变的患病率、心脏病率和表达率。此外，我们探讨了风险因素和结果在LMNA patients.Methods和结果在2003-15，基因检测进行了转介为家族性扩张型心肌病的患者。通过心电图、霍尔特监测、心脏磁共振成像和超声心动图检查LMNA基因型阳性受试者。阳性心脏表型定义为存在房室（AV）传导阻滞、心房颤动/扑动（AF）、室性心动过速（VT）和/或超声心动图DCM。记录心脏移植，并与其他来源的非缺血性DCM进行比较。在561名无关的家族性DCM先证者中，35名（6.2%）有LMNA突变。家庭筛查诊断出另外93名LMNA基因型阳性的家庭成员。我们临床随访了79例LMNA基因型阳性[年龄42 ± 16岁，射血分数（EF）45 ± 13%]，包括44例（56%）VT。无症状的LMNA基因型阳性家族成员（年龄31 ± 15岁）在4.4 ± 2.9年的随访中，新记录的心脏表型的年发病率为9%，心脏衰竭的年发病率为61%（19/31）。10例（32%）发生房室传导阻滞，7例（23%）发生房颤，12例（39%）发生非持续性室性心动过速。在7.8 ± 6.3年的随访中，79例LMNA患者中有15例（19%）进行了心脏移植。在年轻的无症状LMNA基因型阳性家族成员中，频繁发生房室传导阻滞和室性心动过速的心脏复律率较高，这突出了早期家族筛查和心脏病学随访的重要性。近20%的LMNA患者需要心脏移植。
Aims Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients.Methods and results During 2003-15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 +/- 16 years, ejection fraction (EF) 45 +/- 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 +/- 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 +/- 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 +/- 6.3 years of follow-up.Conclusion LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation.