The Cerebellum

, Volume 17, Issue 2, pp 237–242 | Cite as

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
Short Report

Abstract

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.

Keywords

Spinocerebellar ataxia Genetics Intellectual disability Myoclonus Dystonia 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12311_2017_883_Fig3_ESM.gif (126 kb)
ESM 1

Pedigree chart and characteristics of affected members of large Dutch family with c.1054A > C (p.T352P) mutation [4, 13, 14]. (GIF 125 kb).

12311_2017_883_MOESM1_ESM.tif (187 kb)
High resolution image (TIFF 186 kb).

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Masanori Kurihara
    • 1
  • Hiroyuki Ishiura
    • 1
  • Takuya Sasaki
    • 1
  • Juuri Otsuka
    • 1
  • Toshihiro Hayashi
    • 1
  • Yasuo Terao
    • 1
  • Takashi Matsukawa
    • 1
  • Jun Mitsui
    • 1
  • Juntaro Kaneko
    • 2
  • Kazutoshi Nishiyama
    • 2
  • Koichiro Doi
    • 3
  • Jun Yoshimura
    • 3
  • Shinichi Morishita
    • 3
  • Jun Shimizu
    • 1
  • Shoji Tsuji
    • 1
  1. 1.Department of Neurology, Graduate School of MedicineUniversity of TokyoTokyoJapan
  2. 2.Department of NeurologyKitasato University School of MedicineSagamiharaJapan
  3. 3.Department of Computational Biology and Medical Sciences, Graduate School of Frontier SciencesThe University of TokyoChibaJapan

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