Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A
Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A
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DOI：
10.1007/s00109-011-0725-7
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发表时间：
2011-06-01
影响因子：
4.7
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
--
作者：
Wang, Zhi-Qiang;Chen, Xue-Jiao;Wu, Zhi-Ying
多重酰基辅酶A脱氢缺乏症（MADD）是一种影响氨基酸、脂肪酸和胆碱代谢的常染色体隐性遗传疾病，是导致脂质沉积性肌病的常见遗传缺陷。大多数形式的MADD是由电子转移黄素蛋白（ETF）或ETF脱氢酶（ETFDH）缺乏引起的。然而，其分子特征在以往的中国患者的报告中并没有统一的发现。我们从中国南方51个不相关的家系中招募了56例迟发MADD患者，以研究临床表型与分子遗传基础之间的明确相关性。直接测序ETFA、ETFB和ETFDH的所有外显子，包括内含子-外显子边界以及5'和3'非翻译区。ETFDH缺乏的家系占94.1%（48/51）。ETFDH-c. 250 G> A是最常见的突变，代表83.3%（80/96）的高等位基因频率。正常人群中c.250G > A基因携带率为1.35%（7/520）。在ETFDH缺陷患者的肌肉中鉴定到ETFDH的表达显著降低。ETFDH缺乏是中国南方核黄素反应性MADD的主要原因，c.250G > A是一个重要的突变，可作为一种快速、可靠的筛选方法。
Multiple acyl-CoA dehydrogenation deficiency (MADD) is an autosomal recessive disease affecting amino acid, fatty acid, and choline metabolisms and is a common genetic defect responsible for lipid storage myopathy. Most forms of MADD are caused by a deficiency of electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). However, its molecular feature has not been found uniformly in previous reports of Chinese patients. A large cohort of 56 late-onset MADD patients from 51 unrelated pedigrees in southern China was recruited to investigate a clear correlation between clinical phenotype and molecular genetic basis. All exons of ETFA, ETFB, and ETFDH, including the intron-exon boundaries, and 5' and 3' untranslated regions were directly sequenced. ETFDH deficiencies affected 94.1% (48/51) of the pedigrees. ETFDH-c.250G > A is the most common mutation, representing a high allelic frequency of 83.3% (80/96). Carrier frequency of c.250G > A is estimated to be 1.35% (7/520) in the normal population. A significant reduced expression of ETFDH was identified in the muscle of ETFDH-deficient patients. ETFDH deficiency is a major cause of riboflavin-responsive MADD in southern China, and c.250G > A is an important mutation that could be employed as a fast and reliable screening method.