The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation

Authors

  • Shin Hayashi,

    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan
    2. 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan
    3. Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), Saitama, Japan
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  • Seiji Mizuno,

    1. Department of Pediatrics, Central Hospital, Aichi Human Service Center, Kasugai, Japan
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  • Ohsuke Migita,

    1. Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan
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  • Torayuki Okuyama,

    1. Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan
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  • Yoshio Makita,

    1. Education Center, Asahikawa Medical College, Asahikawa, Japan
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  • Akira Hata,

    1. Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan
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  • Issei Imoto,

    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan
    2. 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan
    3. Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), Saitama, Japan
    4. Hard Tissue Genome research Center, Tokyo Medical and Dental University, Tokyo, Japan
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  • Johji Inazawa

    Corresponding author
    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan
    2. 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan
    3. Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), Saitama, Japan
    4. Hard Tissue Genome research Center, Tokyo Medical and Dental University, Tokyo, Japan
    • Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510, Japan.
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  • How to cite this article: Hayashi S, Mizuno S, Migita O, Okuyama T, Makita Y, Hata A, Imoto I, Inazawa J. 2008. The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation. Am J Med Genet Part A 146A:2145–2151.

Abstract

Here we report on a 5-year-old Japanese girl with developmental delay and microcephaly. Although she had a normal karyotype, a bacterial artificial chromosome-based array-comparative genome hybridization analysis detected a de novo 4.0-Mb heterozygous deletion at Xp11.3–p11.4 harboring nine genes. By comparison with a healthy carrier mother of a boy with atypical Norrie disease having a smaller deletion in the same region, we excluded four genes as candidates whose haploinsufficiency would be causative for developmental delay. Among the other five genes, CASK seems to be the most likely candidate for a causative gene, because it is strongly expressed in fetal brain and plays important roles in neural development and synaptic function. We confirmed that the expression of CASK mRNA was decreased in the patient compared with healthy controls and the patient's X-chromosomal inactivation was not skewed. These results suggested that the genetic deletion of CASK results in haploinsufficiency, which might be causative for the patient's developmental delay or mental retardation. © 2008 Wiley-Liss, Inc.

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