Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children
Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children
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DOI：
10.1016/j.nmd.2011.06.005
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发表时间：
2011-11-01
影响因子：
2.8
通讯作者：
Sperl, Wolfgang
中科院分区：
文献类型：
--
作者：
Mayr, Johannes A.;Zimmermann, Franz A.;Sperl, Wolfgang
在一个家庭的三个孩子提出了严重的新生儿乳酸性酸中毒，肥厚型心肌病和全身肌张力减退。一名儿童在婴儿期死亡，两名儿童在临床严重的新生儿期存活。在9岁和17岁时，他们分别表现出运动不耐受、近端肌无力、非进行性肥厚性心肌病和正常的智力发育。在肌肉活检中发现呼吸链酶的正常活性;但线粒体磷酸盐载体的量减少。该蛋白质以两种组织特异性同种型表达，所述两种组织特异性同种型通过SLC 25 A3基因转录物的互斥选择性剪接产生。我们发现了一个纯合突变c.158-9A>G，位于心脏和骨骼肌特异性外显子3A旁边的5 '-内含子中。这产生了一个新的剪接位点，导致野生型等位基因减少95%以上。(C)2011 Elsevier B. V.保留所有权利。
In a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17 years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic cardiomyopathy and normal mental development. In a muscle biopsy normal activity of respiratory chain enzymes was found; however the amount of the mitochondrial phosphate carrier was decreased. This protein is expressed in two tissue-specific isoforms generated by mutually exclusive alternative splicing of the SLC25A3 gene transcript. We identified a homozygous mutation c.158-9A>G located in the 5'-intron next to exon 3A specific for heart and skeletal muscle. This creates a novel splice site resulting in a more than 95% decrease of the wild type allele. (C) 2011 Elsevier B.V. All rights reserved.