Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel.
J Inherit Metab Dis. 2012 Jan;35(1):125-31. doi: 10.1007/s10545-011-9348-y. Epub 2011 May 24.
Defects of the mitochondrial oxidative phosphorylation (OXPHOS) system are frequent causes of neurological disorders in children. Linkage analysis and DNA sequencing identified a new founder p.G250V substitution in the C20ORF7 complex I chaperone in five Ashkenazi Jewish patients from two families with a combined OXPHOS complex I and IV defect presenting with Leigh's syndrome in infancy. Complementation with the wild type gene restored complex I, but only partially complex IV activity. Although the pathogenic mechanism remains elusive, a C20ORF7 defect should be considered not only in isolated complex I deficiency, but also in combination with decreased complex IV. Given the significant 1:290 carrier rate for the p.G250V mutation among Ashkenazi Jews, this mutation should be screened in all Ashkenazi patients with Leigh's syndrome prior to muscle biopsy.
线粒体氧化磷酸化（OXPHOS）系统缺陷是儿童神经紊乱的常见病因。连锁分析和 DNA 测序在两个具有 OXPHOS 复合物 I 和 IV 缺陷的家族中发现了五名来自阿什肯纳兹犹太人的婴儿期莱氏综合征患者中 C20ORF7 复合物 I 伴侣的新的 p.G250V 取代。野生型基因的互补恢复了复合物 I，但仅部分恢复了复合物 IV 的活性。尽管发病机制仍不清楚，但不仅在孤立的复合物 I 缺乏症中，而且在与复合物 IV 减少相结合的情况下，都应考虑 C20ORF7 缺陷。鉴于阿什肯纳兹犹太人中 p.G250V 突变的携带者频率为 1:290，因此在进行肌肉活检之前，应在所有患有莱氏综合征的阿什肯纳兹犹太裔患者中筛查该突变。
