DYNC1H1

Gene product: Cytoplasmic Dynein Heavy Chain 1.

Protein function: This gene encodes a large (over 530 kD) crucial subunit of the cytoplasmic dynein complex，the cytoplasmic dyneins play an important role in intracellular motility, including retrograde axon transport, protein sorting, organelle movement and spindle dynamics [1-2].

Phenotype: Charcot-Marie-Tooth disease, axonal, type 20（AD）[3]；Mental retardation, autosomal dominant 13（AD）(Some children may presented as West syndrome, some may have abnormal brain structure, such as polymicrogyria, lissencephaly, etc) [4-7]；Spinal muscular atrophy, lower extremity-predominant 1（AD）[8].

Mutation database: ClinVar.

Clinical and basic research: PubMed (PMID: 34092403 (Brain Dev. 2021), 34803881 (Front Neurol. 2021), 28325891 (Sci Rep. 2017)).

References:

1. Vaisberg, E.A., M.P. Koonce, and J.R. McIntosh, Cytoplasmic dynein plays a role in mammalian mitotic spindle formation. J Cell Biol, 1993. 123(4): p. 849-58.
2. Poirier, K., et al., Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet, 2013. 45(6): p. 639-47.
3. Weedon, M.N., et al., Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet, 2011. 89(2): p. 308-12.
4. Willemsen, M.H., et al., Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet, 2012. 49(3): p. 179-83.
5. Yang, H., et al., De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms. Front Neurol, 2021. 12: p. 733178.
6. Kolbjer, S., et al., Lissencephaly in an epilepsy cohort: Molecular, radiological and clinical aspects. Eur J Paediatr Neurol, 2021. 30: p. 71-81.
7. Epilepsy Phenome/Genome Project, E.K.C., Diverse genetic causes of polymicrogyria with epilepsy. Epilepsia, 2021. 62(4): p. 973-983.
8. Harms, M.B., et al., Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. Neurology, 2012. 78(22): p. 1714-20.