Malignant mutation in the lamin A/C gene causing progressive conduction system disease and early sudden death in a family with mild form of limb-girdle muscular dystrophy
Malignant mutation in the lamin A/C gene causing progressive conduction system disease and early sudden death in a family with mild form of limb-girdle muscular dystrophy
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DOI：
10.1007/s10840-007-9133-x
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发表时间：
2007-06-01
影响因子：
1.8
通讯作者：
Katritsis, Demosthenes G.
中科院分区：
文献类型：
--
作者：
Antoniades, Loizos;Eftychiou, Christos;Katritsis, Demosthenes G.
背景Lamin蛋白A和C是核膜的主要功能和结构成分。LMNA基因的突变与扩张型心肌病、传导系统缺陷和骨骼肌营养不良同时相关，受累程度各不相同。我们报道了一个层蛋白A/C基因突变家系(c.908-909delCT)。方法对一个先证者家族的35名成员进行临床和遗传学分析。家族成员表现为传导系统缺陷、肢体带状肌营养不良、扩张型心肌病、携带lamin A/C突变或猝死。传导系统缺陷是受累成员的主要特征(67%)，伴有不同程度的扩张型心肌病(33%)和肢体带状肌营养不良(53%)。猝死发生在4名成员(27%)，并在3名受影响成员(20%)的早期表现为特征。突变C.908-909delCT在12名受影响成员中被证实。结论Lamin C.908-909delCT突变与其他扩张型心肌病相关突变相比是恶性的。这种突变的患者房室传导异常进展迅速，猝死可能是其表现特征。在这种情况下，早期识别受影响的家庭和考虑植入除颤器是很重要的。
Background Lamin proteins A and C are major functional and structural components of the nuclear lamina. Mutations of the LMNA gene have been associated with dilated cardiomyopathy, conduction system defects and skeletal muscle dystrophy simultaneously, in variable involvement. We report on a family with a mutation of the lamin A/C gene (c.908-909delCT).Methods Thirty five members of the family of a proband were studied and underwent clinical and genetic evaluation. Family members were considered to be affected if they demonstrated conduction system defects, limb-girdle muscular dystrophy, dilated cardiomyopathy, carried the lamin A/C mutation or suffered sudden death.Results Fifteen members of the family were considered to be affected. Conduction system defects were the major feature of the affected members (67%), with variable involvement of dilated cardiomyopathy (33%), and limb-girdle muscular dystrophy (53%). Sudden death occurred in four members (27%) and was the presenting feature in three (20%) of the affected members at an early age. Mutation c.908-909delCT was confirmed in 12 of the affected members. The pattern of inheritance was autosomal dominant.Conclusion Lamin c.908-909delCT mutation is malignant compared to other dilated cardiomyopathy-associated mutations of the Lamin A/C gene. Patients with this mutation have rapid progression of atrioventricular conduction abnormalities, and sudden death may be the presenting feature. Early identification of affected families and consideration of an implantable defibrillator is important in this setting.