Two cases of DYNC1H1 mutations with intractable epilepsy

Ayumi Matsumoto, Karin Kojima, Fuyuki Miya, Akihiko Miyauchi, Kazuhisa Watanabe, Sadahiko Iwamoto, Kensuke Kawai, Mitsuhiro Kato, Yukitoshi Takahashi, Takanori Yamagata

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot–Marie–Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. Case reports: Patient 1 had severe ID. At the age of 2 months, she presented myoclonic seizures and tonic seizures, and later experienced atonic seizures and focal impaired-awareness seizures (FIAS). EEG showed slow waves in right central areas during myoclonic seizures. Brain MRI revealed pachygyria, predominantly in the occipital lobe. After callosal transection her atonic seizures disappeared, but FIAS remained. Patient 2 was diagnosed with autism spectrum disorder (ASD) and severe ID. At the age of 7 years, he presented generalized tonic–clonic seizures, myoclonic seizures, and FIAS. Interictal EEG showed generalized spike-and-wave complexes, predominantly in the left frontal area. Brain MRI was unremarkable. Exome sequencing revealed novel de novo mutations in DYNC1H1: c.4691A > T, p.(Glu1564Val) in Patient 1 and c.12536 T > C, p.(Leu4179Ser) in Patient 2. Conclusions: DYNC1H1 comprises a stem, stalk, and six AAA domains. Patient 2 is the second report of an AAA6 domain mutation without malformations of cortical development. The p.(Gly4072Ser) mutation in the AAA6 domain was also reported in a patient with ASD. It may be that the AAA6 domain has little effect on neuronal movement of DYNC1H1 along microtubules.

Original languageEnglish
Pages (from-to)857-862
Number of pages6
JournalBrain and Development
Issue number8
Publication statusPublished - 2021 Sept
Externally publishedYes


  • Dynein cytoplasmic 1 heavy chain 1 (DYNC1H1)
  • Epilepsy
  • Lissencephaly
  • Malformations of cortical development (MCD)
  • Pachygyria

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology


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