Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene
Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene
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DOI：
10.1016/s0002-9343(02)01070-7
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发表时间：
2002-05-01
影响因子：
5.9
通讯作者：
Bowcock, AM
中科院分区：
文献类型：
--
作者：
Garg, A;Speckman, RA;Bowcock, AM
目的：LMNA(lamin A/C)基因编码核膜蛋白lamin A和lamin C不同结构域的突变可导致家族性部分脂营养不良(Dunnigan变种)、扩张型心肌病以及常染色体显性表型Emery-Dreifuss和四肢带状肌营养不良。本研究的目的是检测两个家族性部分性脂营养不良(Dunnigan变异型)家系中的LMNA变异，这些家系还伴有心脏传导系统缺陷和其他与心肌病相关的表现。方法：采用脱氧核糖核酸测序的方法对两个家族性部分性脂肪营养不良家族性脂肪营养不良家系的LMNA变异进行分析。一个突变R28W(CGG-->；TGG)影响氨基末端头部区域，另一个突变R62G(CGC-->；GGC)影响α螺旋杆状结构域。来自这两个家族的受试者都有更多的心脏症状，如房室传导缺陷、房颤、因脑室扩张和植入起搏器而导致的心力衰竭。其中一个家系的先证者也有近端肌肉无力。结论：在两个具有Dunnigan变异型家族性部分脂营养不良、心脏传导系统缺陷和其他与心肌病相关的表现的家系中，LMNA基因的新的遗传缺陷表明由于LMNA突变而发生了多系统营养不良综合征。
PURPOSE: Mutations in different domains of the LMNA (lamin A/C) gene encoding nuclear envelope proteins lamin A and lamin C cause familial partial lipodystrophy (Dunnigan variety), dilated cardiomopathy, and autosomal dominant forms of Emery-Dreifuss and limb-girdle muscular dystrophies. The objective of this study was to evaluate LMNA variants in two families with familial partial lipodystrophy (Dunnigan variety) who also had cardiac conduction system defects and other manifestations related to cardiomyopathy.METHODS: We performed mutational analysis of the lamin A/C gene in affected and unaffected subjects by deoxyribonucleic acid sequencing of the exons.RESULTS: Two novel missense mutations were identified in exon 1 of the lamin A/C gene. One mutation, R28W (CGG-->TGG), affected the amino-terminal head domain, and the other, R62G (CGC-->GGC), affected the alpha-helical rod domain. Affected subjects from both families had an increased prevalence of cardiac manifestations, such as atrioventricular conduction defects, atrial fibrillation, and heart failure due to ventricular dilatation, as well as pacemaker implantation. The proband from one of the families also had proximal muscle weakness.CONCLUSION: Novel genetic defects in the LMNA gene in two families with the Dunnigan variety of familial partial lipodystrophy, cardiac conduction system defects, and other manifestations related to cardiomyopathy suggest the occurrence of a multisystem dystrophy syndrome due to LMNA mutations.