期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 92, 期 5, 页码 774-780出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2013.04.006
关键词
-
资金
- Australian Research Council
- National Institute of Neurologic Disorders and Stroke, National Institutes of Health [1K08NS060695]
- Myelin Disorders Bioregistry Project
- Mission Massimo Foundation
- Victorian State Government Operational Infrastructure Support Program
- Institute for Molecular Bioscience funds
- NeCTAR Genomics Virtual Lab
- University of Queensland Foundation Research Excellence Award
- ZonMw TOP [91211005]
Inherited white-matter disorders are a broad class of diseases for which treatment and classification are both challenging. Indeed, nearly half of the children presenting with a leukoencephalopathy remain without a specific diagnosis. Here, we report on the application of high-throughput genome and exome sequencing to a cohort of ten individuals with a leukoencephalopathy of unknown etiology and clinically characterized by hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL), as well as the identification of compound-heterozygous and homozygous mutations in cytoplasmic aspartyl-tRNA synthetase (DARS). These mutations cause nonsynonymous changes to seven highly conserved amino acids, five of which are unchanged between yeast and man, in the DARS C-terminal lobe adjacent to, or within, the active-site pocket. Intriguingly, HBSL bears a striking resemblance to leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate (LBSL), which is caused by mutations in the mitochondria-specific DARS2, suggesting that these two diseases might share a common underlying molecular pathology. These findings add to the growing body of evidence that mutations in tRNA synthetases can cause a broad range of neurologic disorders.
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