title: Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development.
abstract: 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.
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Li
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Niu
authors.initials: N
authors.lastname: Li
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yu
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Ru-En
authors.initials: RE
authors.lastname: Yao
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.|2 Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: 1 Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D056445:Cytoplasmic Dyneins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D054220:Malformations of Cortical Development / Q000000981:diagnostic imaging / Q000235:genetics*; D009134:Muscular Atrophy, Spinal / Q000000981:diagnostic imaging / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: C511240:DYNC1H1 protein, human; D056445:Cytoplasmic Dyneins
keywords: DYNC1H1; cytoplasmic dynein.; exome sequencing; malformations of cortical development; spinal muscular atrophy with lower extremity predominance