Key result
Exome sequencing identified a novel de novo heterozygous missense mutation c.3395G>A and a previously reported mutation c.10151G>A in the DYNC1H1 gene in two girls with neurologic diseases.
Case Report (n=2)
Exome sequencing identified novel and previously reported de novo DYNC1H1 mutations in two pediatric patients with neurologic disorders, expanding the mutational spectrum of the gene.
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May support expanded DYNC1H1 testing in unexplained pediatric neurology; extends variant spectrum but remains hypothesis-generating.
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.
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Chen et al. (2016) conducted a case report in Spinal muscular atrophy and malformations of cortical development (n=2). De novo DYNC1H1 mutations was evaluated on Identification of causative genetic variants. Exome sequencing identified a novel de novo heterozygous missense mutation c.3395G>A and a previously reported mutation c.10151G>A in the DYNC1H1 gene in two girls with neurologic diseases.
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