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Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan

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Abstract

A nationwide survey was conducted for identifying ataxia-telangiectasia (AT) patients in Japan. Eighty-nine patients were diagnosed between 1971 and 2006. Detailed clinical and laboratory data of 64 patients including affected siblings were collected. Analyses focused on malignancy, therapy-related toxicity, infection, and hematological/immunological parameters. The phenotypic variability of AT was assessed by comparing 26 affected siblings from 13 families. Malignancy developed in 22% of the cases and was associated with a high rate of severe therapy-related complications: chemotherapy-related cardiac toxicity in 2 children, and severe hemorrhagic cystitis requiring surgery in 2 patients. The frequency of serious viral infections correlated with the T cell count. Hypogammaglobulinemia with hyper-IgM (HIGM) was recorded in 5 patients, and 3 patients developed panhypogammaglobulinemia. Differences in immunological parameters were noted in siblings. Four patients showed an HIGM phenotype, in contrast to their siblings with normal IgG and IgM levels. The patients with HIGM phenotype showed reduced levels of TRECs and CD27+CD20+ memory B cells. The findings suggest that hitherto unidentified modifier genes or exogenous environmental factors can influence the overall immune responses. Our data along with future prospective study will lead to better understanding of the hematological/immunological phenotypes and to better care of the patients.

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Acknowledgments

This work was in part supported by grants from the Ministry of Health, Labour, and Welfare and from the Ministry of Education, Culture, Sports, Science, and Technology to SM and TM.

Conflict of interest statement

We have no financial relationships or conflict of interest relevant to this manuscript to be disclosed.

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Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Tomohiro Morio, Naomi Takahashi, Fumiaki Watanabe, Fumiko Honda, Masaki Sato, Masatoshi Takagi & Shuki Mizutani

  2. Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan

    Ken-ichi Imadome

  3. Department of Pediatrics, Toyama University School of Medicine, Toyama, Japan

    Toshio Miyawaki

  4. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

    Domenico Delia

  5. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Kotoka Nakamura & Richard A. Gatti

Authors
  1. Tomohiro Morio
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  2. Naomi Takahashi
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  3. Fumiaki Watanabe
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  4. Fumiko Honda
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  5. Masaki Sato
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  6. Masatoshi Takagi
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  7. Ken-ichi Imadome
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  9. Domenico Delia
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  10. Kotoka Nakamura
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  11. Richard A. Gatti
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  12. Shuki Mizutani
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Correspondence to Tomohiro Morio.

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Morio, T., Takahashi, N., Watanabe, F. et al. Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan. Int J Hematol 90, 455–462 (2009). https://doi.org/10.1007/s12185-009-0408-0

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  • DOI: https://doi.org/10.1007/s12185-009-0408-0

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