Novel lamin A/C mutations in two families with dilated cardiomyopathy and conduction system disease
Novel lamin A/C mutations in two families with dilated cardiomyopathy and conduction system disease
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DOI：
10.1054/jcaf.2001.26339
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发表时间：
2001-09-01
影响因子：
6
通讯作者：
Hershberger, RE
中科院分区：
文献类型：
--
作者：
Jakobs, PM;Hanson, EL;Hershberger, RE
背景：LMNA基因是与家族性扩张型心肌病有关的6个常染色体病基因之一，编码层蛋白A和C，可选择性剪接核膜蛋白。方法与结果：发现2个常染色体显性遗传性扩张型家族性扩张型心肌病和传导系统疾病的4代白人家族性疾病。在A家系中，在14名成年受试者中发现一种错义突变(核苷酸G607A，氨基酸E203K)，疾病表现为进行性传导性疾病。死亡是由心力衰竭引起的。在B家族中，在10名成人受试者中发现了无义突变(核苷酸C673T，氨基酸R225X)；该病也表现为进行性传导性疾病，但起病较早(30年和40年)，室性心律失常，左心室增大和收缩功能障碍。死亡原因是心力衰竭和心源性猝死。两个家系均未发现骨骼肌病。结论：Lamin A/C新的杆状片段突变可导致可变传导系统疾病和扩张型心肌病而不伴有骨骼肌病。
Background: The LMNA gene, one of 6 autosomal disease genes implicated in familial dilated cardiomyopathy, encodes lamins A and C, alternatively spliced nuclear envelope proteins. Mutations in lamin A/C cause 4 diseases: Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, Dunnigan-type familial partial lipodystrophy, and dilated cardiomyopathy.Methods and Results: Two 4-generation white families with autosomal dominant familial dilated cardiomyopathy and conduction system disease were found to have novel mutations in the rod segment of lamin A/C. In family A a missense mutation (nucleotide G607A, amino acid E203K) was identified in 14 adult subjects; disease was manifest as progressive conduction disease in the fourth and fifth decades. Death was caused by heart failure. In family B a nonsense mutation (nucleotide C673T, amino acid R225X) was identified in 10 adult subjects; disease was also manifest as progressive conduction disease but with earlier onset (third and fourth decades), ventricular dysrhythmias, left ventricular enlargement, and systolic dysfunction. Death was caused by heart failure and sudden cardiac death. Skeletal muscle disease was not observed in either family.Conclusions: Novel rod segment mutations in lamin A/C cause variable conduction system disease and dilated cardiomyopathy without skeletal myopathy.