Human Genetics

, Volume 131, Issue 1, pp 99–110

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

Authors

  • Shin Hayashi
    • Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical ScienceTokyo Medical and Dental University
    • Hard Tissue Genome Research Center, Tokyo Medical and Dental University
  • Nobuhiko Okamoto
    • Department of Planning and ResearchOsaka Medical Center and Research Institute for Maternal and Child Health
  • Yasutsugu Chinen
    • Department of PediatricsUniversity of the Ryukyu School of Medicine
  • Jun-ichi Takanashi
    • Department of PediatricsKameda Medical Center
  • Yoshio Makita
    • Education Center, Asahikawa Medical College
  • Akira Hata
    • Department of Public HealthChiba University Graduate School of Medicine
  • Issei Imoto
    • Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical ScienceTokyo Medical and Dental University
    • Department of Human Genetics and Public Health Graduate School of Medical ScienceThe University of Tokushima
    • Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical ScienceTokyo Medical and Dental University
    • Global Center of Excellence (GCOE) Program for ‘International Research Center for Molecular Science in Tooth and Bone Diseases’Tokyo Medical and Dental University
Original Investigation

DOI: 10.1007/s00439-011-1047-0

Cite this article as:
Hayashi, S., Okamoto, N., Chinen, Y. et al. Hum Genet (2012) 131: 99. doi:10.1007/s00439-011-1047-0

Abstract

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.

Supplementary material

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

Copyright information

© Springer-Verlag 2011