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Journal of Neurology

, Volume 262, Issue 5, pp 1278–1284 | Cite as

Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene

  • Masayuki SasakiEmail author
  • Chihiro Ohba
  • Mizue Iai
  • Shinichi Hirabayashi
  • Hitoshi Osaka
  • Takuya Hiraide
  • Hirotomo Saitsu
  • Naomichi Matsumoto
Original Communication

Abstract

Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) have been identified in families with early-onset spinocerebellar ataxia type 29 (SCA29) and late-onset SCA15, but have not been found in sporadic infantile-onset cerebellar ataxia. We examined if mutations of ITPR1 are also involved in sporadic infantile-onset SCA. Sixty patients with childhood-onset cerebellar atrophy of unknown etiology and their families were examined by whole-exome sequencing. We found de novo heterozygous ITPR1 missense mutations in four unrelated patients with sporadic infantile-onset, nonprogressive cerebellar ataxia. Patients displayed nystagmus, tremor, and hypotonia from very early infancy. Nonprogressive ataxia, motor delay, and mild cognitive deficits were common clinical findings. Brain magnetic resonance imaging revealed slowly progressive cerebellar atrophy. ITPR1 missense mutations cause infantile-onset cerebellar ataxia. ITPR1-related SCA includes sporadic infantile-onset cerebellar ataxia as well as SCA15 and SCA29.

Keywords

Spinocerebellar ataxia type 15/29 (SCA15/29) Infantile-onset Whole-exome sequencing (WES) Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) ITPR1-related SCA 

Notes

Acknowledgments

We thank all the patients and their families for their participation in this study. This study was supported by the Ministry of Health, Labor and Welfare of Japan [Research Grant for Nervous and Mental Disorders (24-7)]; the Japan Society for the Promotion of Science [Grant-in-Aid for Scientific Research (B; 25293085), a Grant-in-Aid for challenging Exploratory Research (26670505), and a Grant-in-Aid for Scientific Research (A) (13313587)]; the Takeda Science Foundation; the fund for the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency; the Strategic Research Program for Brain Sciences (11105137); and a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (12024421).

Conflicts of interest

The authors have no disclosures to report that are related to this manuscript.

Ethical standard

Approval was obtained from the local ethical standards committee on human experimentation and written informed consent from all subjects before enrolment. The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Masayuki Sasaki
    • 1
    Email author
  • Chihiro Ohba
    • 2
  • Mizue Iai
    • 3
  • Shinichi Hirabayashi
    • 4
  • Hitoshi Osaka
    • 3
    • 5
  • Takuya Hiraide
    • 1
  • Hirotomo Saitsu
    • 2
  • Naomichi Matsumoto
    • 2
  1. 1.Department of Child NeurologyNational Center of Neurology and PsychiatryKodairaJapan
  2. 2.Department of Human GeneticsYokohama City University Graduate School of MedicineYokohamaJapan
  3. 3.Department of NeurologyKanagawa Children Medical CenterYokohamaJapan
  4. 4.Department of NeurologyNagano Children’s HospitalAzuminoJapan
  5. 5.Department of PediatricsJichi Medical SchoolTochigiJapan

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