Original Article

Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis

  • Journal of Human Genetics (2010) 55, 590599 (2010)
  • doi:10.1038/jhg.2010.74
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This work is part of an ongoing study by the Japanese Mental Retardation Research Consortium.

Abstract

X-linked mental retardation (XLMR) is a common, clinically complex and genetically heterogeneous disease arising from many mutations along the X chromosome. Although research during the past decade has identified >90 XLMR genes, many more remain uncharacterized. In this study, copy-number variations (CNVs) were screened in individuals with MR from 144 families by array-based comparative genomic hybridization (aCGH) using a bacterial artificial chromosome-based X-tiling array. Candidate pathogenic CNVs (pCNVs) were detected in 10 families (6.9%). Five of the families had pCNVs involving known XLMR genes, duplication of Xq28 containing MECP2 in three families, duplication of Xp11.22-p11.23 containing FTSJ1 and PQBP1 in one family, and deletion of Xp11.22 bearing SHROOM4 in one family. New candidate pCNVs were detected in five families as follows: identical complex pCNVs involved in dup(X)(p22.2) and dup(X)(p21.3) containing part of REPS2, NHS and IL1RAPL1 in two unrelated families, duplication of Xp22.2 including part of FRMPD4, duplication of Xq21.1 including HDX and deletion of Xq24 noncoding region in one family, respectively. Both parents and only mother samples were available in six and three families, respectively, and pCNVs were inherited from each of their mothers in those families other than a family of the proband with deletion of SHROOM4. This study should help to identify the novel XLMR genes and mechanisms leading to MR and reveal the clinical conditions and genomic background of XLMR.

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Acknowledgements

We thank the patients and families for their generous participation in this study, N Murakami for cell culture and EBV-transformation, and M Kato, A Takahashi and R Mori for technical assistance. This work is supported by grants-in-aid for Scientific Research on Priority Areas and Global Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone from the Ministry of Education, Culture, Sports, Science and Technology, Japan; a grant from the New Energy and Industrial Technology Development Organization (NEDO); and, in part, by a research grant for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare, Japan. This study was supported by the Joint Usage/Research of Medical Research Institute, Tokyo Medical Dental University. S Honda is supported by Research Fellowship of the Japan Society for the Promotion of Science (JSPS) for Young Scientists.

Author information

Affiliations

  1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan

    • Shozo Honda
    • , Shin Hayashi
    • , Issei Imoto
    •  & Johji Inazawa
  2. Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan

    • Issei Imoto
    •  & Johji Inazawa
  3. Department of Pediatrics, Okinawa Child Development Center, Okinawa, Japan

    • Jun Toyama
  4. Department of Neuropathology, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan

    • Hitoshi Okazawa
  5. Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan

    • Eiji Nakagawa
    •  & Yu-ichi Goto
  6. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, NCNP, Tokyo, Japan

    • Eiji Nakagawa
    •  & Yu-ichi Goto
  7. Grobal Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan

    • Johji Inazawa
  8. See Appendix.

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Corresponding author

Correspondence to Johji Inazawa.

Supplementary information

Appendices

Appendix

Yu-ichi Goto, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Johji Inazawa, Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan; Mitsuhiro Kato, Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan; Takeo Kubota, Department of Epigenetic Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan; Kenji Kurosawa, Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan; Naomichi Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Eiji Nakagawa, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Eiji Nanba, Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago, Japan; Hitoshi Okazawa, Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Shinji Saitoh, Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Takahito Wada, Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.