Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase
Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase
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DOI：
10.1038/ejhg.2010.83
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发表时间：
2010-10-01
影响因子：
5.2
通讯作者：
Parvari, Ruti
中科院分区：
文献类型：
--
作者：
Levitas, Aviva;Muhammad, Emad;Parvari, Ruti
心肌病是导致心力衰竭的常见疾病；最常见的形式是扩张型心肌病(DCM)，其特征是左或双室扩张和收缩功能受损。扩张型心肌病导致相当大的发病率和死亡率，是心源性猝死的主要原因之一。尽管大约三分之一的患者被报道患有遗传性扩张型心肌病，但已报道的突变只解释了一小部分家族性扩张性心肌病。此外，隐性新生儿DCM分离型很少与突变相关。在这项研究中，我们提出了SDHA基因突变与隐性新生儿分离的DCM的关联，该患者来自两个有血缘关系的贝都因大家族。心肌病可能是由于心肌中SDH酶活性的显著组织特异性降低所致，而骨骼肌和淋巴母细胞中仍有大量的SDH酶活性。值得注意的是，此前有报道称，相同的突变会导致多系统衰竭，导致新生儿死亡和Leigh综合征。这项研究对一种严重形式的新生儿心肌病的分子特征做出了贡献，并强调了编码线粒体呼吸链蛋白的核基因的特定错义突变导致的极端表型变异。《欧洲人类遗传学杂志》(2010年)1811601165；DOI：10.1038/ejhg.2010.83；2010年6月16日在线出版
Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain. European Journal of Human Genetics (2010) 18, 1160-1165; doi: 10.1038/ejhg.2010.83; published online 16 June 2010