SDHA Mutation with Dominant Transmission Results in Complex II Deficiency with Ocular, Cardiac, and Neurologic Involvement
SDHA Mutation with Dominant Transmission Results in Complex II Deficiency with Ocular, Cardiac, and Neurologic Involvement
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DOI：
10.1002/ajmg.a.37986
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发表时间：
2017-01-01
影响因子：
2
通讯作者：
Schaller, Andre
中科院分区：
文献类型：
--
作者：
Courage, Carolina;Jackson, Christopher B.;Schaller, Andre
线粒体呼吸复合物 II（琥珀酸脱氢酶，SDH）的孤立缺陷很少见，约占所有呼吸链缺陷诊断的 2%。在此，我们报告了对三个家族成员的临床和分子研究，该家族成员的大黄素蛋白亚基 SDHA 存在杂合突变，先前描述该突变会导致复合物 II 缺陷。指标患者出现双侧视神经萎缩和眼球运动障碍、进行性多发性神经病、精神受累和心肌病。他的两个孩子在儿童早期就出现了心肌病和甲基戊烯酸尿症。女儿7个月大时因心功能不全去世。 30岁的儿子患有心肌病，成年后出现双眼视神经萎缩。在构成复合物 II (SDHA、SDHB、SDHC、SDHD) 的四种核编码蛋白和目前已知的组装因子 SDHAF1 和 SDHAF2 中，SDHA、SDHB、SDHD 和 SDHAF1 中主要是隐性遗传突变，已被描述为导致线粒体疾病表型的原因。这是第二份展示 SDHA 突变常染色体显性遗传的报告。
Isolated defects of the mitochondrial respiratory complex II (succinate dehydrogenase, SDH) are rare, accounting for approximately 2% of all respiratory chain deficiency diagnoses. Here, we report clinical and molecular investigations of three family members with a heterozygous mutation in the large flavoprotein subunit SDHA previously described to cause complex II deficiency. The index patient presented with bilateral optic atrophy and ocular movement disorder, a progressive polyneuropathy, psychiatric involvement, and cardiomyopathy. Two of his children presented with cardiomyopathy and methylglutaconic aciduria in early childhood. The daughter deceased at the age of 7 months due to cardiac insufficiency. The 30-year old son presents with cardiomyopathy and developed bilateral optic atrophy in adulthood. Of the four nuclear encoded proteins composing complex II (SDHA, SDHB, SDHC, SDHD) and currently known assembly factors SDHAF1 and SDHAF2 mainly recessively inherited mutations have been described in SDHA, SDHB, SDHD, and SDHAF1 to be causative for mitochondrial disease phenotypes. This is the second report presenting autosomal dominant inheritance of a SDHA mutation.