Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development
| Autor: | Guoqiang Li, Jian Wang, Ruen Yao, Niu Li, Yiping Shen, Xiumin Wang, Yulin Chen, Tingting Yu, Yufei Xu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytoplasmic dynein Cytoplasmic Dyneins Heterozygote DNA Mutational Analysis Mutation Missense Distal spinal muscular atrophy Bioinformatics Muscular Atrophy Spinal 03 medical and health sciences 0302 clinical medicine medicine Spinal muscular atrophy with lower extremity predominance Humans Exome Gene Exome sequencing business.industry Brain Infant medicine.disease Malformations of Cortical Development 030104 developmental biology Phenotype Pediatrics Perinatology and Child Health Female Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Journal of child neurology. 32(4) |
| ISSN: | 1708-8283 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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