当前位置: X-MOL 学术Eur. J. Hum. Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A recurrent de novo ATP5F1A substitution associated with neonatal complex V deficiency
European Journal of Human Genetics ( IF 5.2 ) Pub Date : 2021-09-06 , DOI: 10.1038/s41431-021-00956-0
Matthew A Lines 1, 2 , Alexanne Cuillerier 3 , Pranesh Chakraborty 4, 5, 6 , Turaya Naas 6 , M Laura Duque Lasio 7 , Jean Michaud 8 , Chantal Pileggi 3 , Mary-Ellen Harper 3 , Yan Burelle 3, 9 , Tomi L Toler 7 , Neal Sondheimer 10, 11, 12 , Heather P Crawford 13 , Francisca Millan 14 , Michael T Geraghty 4, 5
Affiliation  

Mitochondrial disorders are a heterogeneous group of rare, degenerative multisystem disorders affecting the cell’s core bioenergetic and signalling functions. Spontaneous improvement is rare. We describe a novel neonatal-onset mitochondriopathy in three infants with failure to thrive, hyperlactatemia, hyperammonemia, and apparent clinical resolution before 18 months. Exome sequencing showed all three probands to be identically heterozygous for a recurrent de novo substitution, c.620G>A [p.(Arg207His)] in ATP5F1A, encoding the α-subunit of complex V. Patient-derived fibroblasts exhibited multiple deficits in complex V function and expression in vitro. Structural modelling predicts the observed substitution to create an abnormal region of negative charge on ATP5F1A’s β-subunit-interacting surface, adjacent to the nearby β subunit’s active site. This disorder, which presents with life-threatening neonatal manifestations, appears to follow a remitting course; the long-term prognosis remains unknown.



中文翻译:

与新生儿复合物 V 缺乏相关的复发性从头 ATP5F1A 替代

线粒体疾病是一组罕见的退行性多系统疾病,影响细胞的核心生物能量和信号传导功能。自发的改善很少见。我们在三名婴儿中描述了一种新的新生儿发病的线粒体病,这些婴儿在 18 个月前无法茁壮成长、高乳酸血症、高氨血症和明显的临床消退。外显子组测序显示所有三个先证者对于 ATP5F1A 中的复发性从头取代 c.620G>A [p.(Arg207His)] 是相同的杂合子,编码复合体 V 的 α 亚基。患者来源的成纤维细胞在体外复合体 V 功能和表达方面表现出多重缺陷。结构模型预测观察到的取代会在 ATP5F1A 的 β-亚基相互作用表面上产生一个异常的负电荷区域,与附近的 β 亚基的活性位点相邻。这种疾病表现为危及生命的新生儿表现,似乎有一个缓解的过程;长期预后仍然未知。

更新日期:2021-09-06
down
wechat
bug