期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 89, 期 1, 页码 28-43出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2011.05.017
关键词
-
资金
- CCTS at the University of Utah [UL1RR025764]
- National Cancer Institute [P30CA042014]
- Research Council of Norway [197136]
- Norwegian Cancer Society
- National Human Genome Research Institute (NHGRI) [1RC2HG005619]
- NIH/National Center for Research Resources [UL1 RR025774]
- NIH/NHGRI [K99HG005846]
- NHGRI [5R01HG5692]
- NHGRI, NIH
We have identified two families with a previously undescribed lethal X-linked disorder of infancy; the disorder comprises a distinct combination of an aged appearance, craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, and cardiac arrhythmias. Using X chromosome exon sequencing and a recently developed probabilistic algorithm aimed at discovering disease-causing variants, we identified in one family a c.109T>C (p.Ser37Pro) variant in NAA 10, a gene encoding the catalytic subunit of the major human N-terminal acetyltransferase (NAT). A parallel effort on a second unrelated family converged on the same variant. The absence of this variant in controls, the amino acid conservation of this region of the protein, the predicted disruptive change, and the co-occurrence in two unrelated families with the same rare disorder suggest that this is the pathogenic mutation. We confirmed this by demonstrating a significantly impaired biochemical activity of the mutant hNaa10p, and from this we conclude that a reduction in acetylation by hNaa10p causes this disease. Here we provide evidence of a human genetic disorder resulting from direct impairment of N-terminal acetylation, one of the most common protein modifications in humans.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据