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家族性扩张型心肌病继发于肌营养不良蛋白剪接位点突变。

Familial dilated cardiomyopathy secondary to dystrophin splice site mutation.

机构信息

Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.

出版信息

J Card Fail. 2010 Mar;16(3):194-9. doi: 10.1016/j.cardfail.2009.11.009.

Abstract

BACKGROUND

Idiopathic dilated cardiomyopathy (DCM) encompasses a heterogeneous group of disorders, posing significant diagnostic challenges. Genetic etiologies underlie an important subset of DCM, including 20 genes and 5 X-linked disorders to date. We report a family with a rare dystrophin gene alteration, identified after evaluation of asymptomatic children whose extended family history included cardiomyopathy, premature cardiac death, or cardiac transplantation.

METHODS AND RESULTS

Record review, clinical evaluations, and DNA samples were obtained from members of a 5-generation pedigree with early onset DCM. Five of 6 affected males experienced death or cardiac transplant in their second or third decades. No affected individuals had skeletal muscle weakness before acute cardiac decompensation. Dystrophin gene analysis of an affected family member revealed sequence alteration at the conserved 5' splice site of exon 1 of the muscle-specific isoform of dystrophin (IVS1 +1 G>T) and co-segregated with cardiac disease in this family.

CONCLUSIONS

Young males presenting with apparent isolated cardiomyopathy or acute myocarditis may harbor dystrophin mutations without overt skeletal muscle pathology. The etiology of familial risk was not evident in this pedigree before retrospective cardiovascular genetics assessment, highlighting ongoing diagnostic challenges and limitations of standardized screening panels (which do not include dystrophin) in patients with "idiopathic" DCM.

摘要

背景

特发性扩张型心肌病(DCM)包含一组异质性疾病,对诊断构成重大挑战。迄今为止,遗传病因构成了 DCM 的一个重要亚组,包括 20 个基因和 5 个 X 连锁疾病。我们报告了一个家族的罕见肌营养不良基因突变,该家族在评估有扩张型心肌病、心脏性猝死或心脏移植家族史的无症状儿童后发现。

方法和结果

从一个有早发性 DCM 的 5 代家系中获得了记录回顾、临床评估和 DNA 样本。6 名受影响的男性中有 5 名在 20 或 30 岁出头时经历了死亡或心脏移植。在急性心脏失代偿之前,没有受影响的个体有骨骼肌无力。对一个受影响的家族成员的肌营养不良基因突变分析显示,肌肉特异性同工型肌营养不良的第 1 外显子的保守 5' 剪接位点的序列改变(IVS1 +1 G>T),并在家系中与心脏疾病共分离。

结论

年轻男性表现为明显孤立性心肌病或急性心肌炎,可能携带肌营养不良突变而无明显骨骼肌病理。在进行回顾性心血管遗传学评估之前,这个家系的家族风险病因并不明显,突出了在“特发性”DCM 患者中,标准筛查小组(不包括肌营养不良)存在持续的诊断挑战和局限性。

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