Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development
Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development
复制标题
外显子组测序鉴定出与远端脊髓肌肉萎缩和皮质发育畸形相关的从头 DYNC1H1 突变
DOI：
10.1177/0883073816683083
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发表时间：
2017-03-01
影响因子：
1.9
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Chen, Yulin;Xu, Yufei;Wang, Jian
Exome sequencing has become a formidable tool for identifying potential de novo variants in causative genes of human diseases, such as neurodegenerative disorders. This article describes a 16-month-old girl with spinal muscular atrophy with lower extremity predominance and a 13-month-old girl with malformations of cortical development. Exome sequencing identified a novel de novo heterozygous missense mutation c.3395G>A (p.Gly1132Glu) and a previously reported de novo heterozygous missense mutation c.10151G>A (p.Arg3384Gln) in the DYNC1H1 gene. Bioinformatics predictions for c.3395G>A and c.10151G>A indicated pathogenicity of the mutations. DYNC1H1 is a pivotal component of cytoplasmic dynein complex, which is a microtubule-related motor involved in retrograde transport. Previous studies indicated that mutant dynein showed decreased run-length of the motor proteins and diminished retrograde transport, which were clearly associated with neuronal death and neurologic diseases. The present findings expand the mutational spectrum of the DYNC1H1 gene, reemphasizing the significance of the DYNC1H1 protein in the functioning of neurons.
