Human Genetics

, Volume 131, Issue 1, pp 99–110 | Cite as

Novel intragenic duplications and mutations of CASK in patients with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH)

  • Shin Hayashi
  • Nobuhiko Okamoto
  • Yasutsugu Chinen
  • Jun-ichi Takanashi
  • Yoshio Makita
  • Akira Hata
  • Issei Imoto
  • Johji InazawaEmail author
Original Investigation


The CASK gene encoding a member of the membrane-associated guanylate kinase protein family is highly expressed in the mammalian nervous system of both adults and fetuses, playing several roles in neural development and synaptic function. Recently, CASK aberrations caused by both mutations and deletions have been reported to cause severe mental retardation (MR), microcephaly and disproportionate pontine and cerebellar hypoplasia (MICPCH) in females. Here, mutations and copy numbers of CASK were examined in ten females with MR and MICPCH, and the following changes were detected: nonsense mutations in three cases, a 2-bp deletion in one case, mutations at exon–intron junctions in two cases, heterozygous deletions encompassing CASK in two cases and interstitial duplications in two cases. Except for the heterozygous deletions, each change including the intragenic duplications potentially caused an aberrant transcript, resulting in CASK null mutations. The results provide novel mutations and copy number aberrations of CASK, causing MR with MICPCH, and also demonstrate the similarity of the phenotypes of MR with MICPCH regardless of the CASK mutation.


Mental Retardation Bacterial Artificial Chromosome Prime Combination Premature Stop Codon Splice Acceptor Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Ayako Takahashi and Rumi Mori for technical assistance. This study was supported by the Joint Usage/Research Program of Medical Research Institute, Tokyo Medical and Dental University. This work was also supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST); a grant from the New Energy and Industrial Technology Development Organization (NEDO).

Supplementary material

439_2011_1047_MOESM1_ESM.pdf (178 kb)
Supplementary material 1 (PDF 396 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shin Hayashi
    • 1
    • 2
  • Nobuhiko Okamoto
    • 3
  • Yasutsugu Chinen
    • 4
  • Jun-ichi Takanashi
    • 5
  • Yoshio Makita
    • 6
  • Akira Hata
    • 7
  • Issei Imoto
    • 1
    • 8
  • Johji Inazawa
    • 1
    • 9
    Email author
  1. 1.Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical ScienceTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Hard Tissue Genome Research Center, Tokyo Medical and Dental UniversityTokyoJapan
  3. 3.Department of Planning and ResearchOsaka Medical Center and Research Institute for Maternal and Child HealthOsakaJapan
  4. 4.Department of PediatricsUniversity of the Ryukyu School of MedicineOkinawaJapan
  5. 5.Department of PediatricsKameda Medical CenterChibaJapan
  6. 6.Education Center, Asahikawa Medical CollegeAsahikawaJapan
  7. 7.Department of Public HealthChiba University Graduate School of MedicineChibaJapan
  8. 8.Department of Human Genetics and Public Health Graduate School of Medical ScienceThe University of TokushimaTokushimaJapan
  9. 9.Global Center of Excellence (GCOE) Program for ‘International Research Center for Molecular Science in Tooth and Bone Diseases’Tokyo Medical and Dental UniversityTokyoJapan

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