Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia

Masanori Kurihara, Hiroyuki Ishiura, Takuya Sasaki, Juuri Otsuka, Toshihiro Hayashi, Yasuo Terao, Takashi Matsukawa, Jun Mitsui, Juntaro Kaneko, Kazutoshi Nishiyama, Koichiro Doi, Jun Yoshimura, Shinichi Morishita, Jun Shimizu, Shoji Tsuji

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Spinocerebellar ataxia 19/22 (SCA19/22) is a rare type of autosomal dominant SCA that was previously described in 11 families. We report the case of a 30-year-old Japanese man presenting with intellectual disability, early onset cerebellar ataxia, myoclonus, and dystonia without a family history. MRI showed cerebellar atrophy, and electroencephalograms showed paroxysmal sharp waves during hyperventilation and photic stimulation. Trio whole-exome sequencing analysis of DNA samples from the patient and his parents revealed a de novo novel missense mutation (c.1150G>A, p.G384S) in KCND3, the causative gene of SCA19/22, substituting for evolutionally conserved glycine. The mutation was predicted to be functionally deleterious by bioinformatic analysis. Although pure cerebellar ataxia is the most common clinical feature in SCA19/22 families, extracerebellar symptoms including intellectual disability and myoclonus are reported in a limited number of families, suggesting a genotype–phenotype correlation for particular mutations. Although autosomal recessive diseases are more common in patients with early onset sporadic cerebellar ataxia, the present study emphasizes that such a possibility of de novo mutation should be considered.

Original languageEnglish
Pages (from-to)237-242
Number of pages6
Issue number2
Publication statusPublished - 2018 Apr 1
Externally publishedYes


  • Dystonia
  • Genetics
  • Intellectual disability
  • Myoclonus
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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