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

Tomohiro Morio, Naomi Takahashi, Fumiaki Watanabe, Fumiko Honda, Masaki Sato, Masatoshi Takagi, Ken Ichi Imadome, Toshio Miyawaki, Domenico Delia, Kotoka Nakamura, Richard A. Gatti, Shuki Mizutani

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)455-462
Number of pages8
JournalInternational Journal of Hematology
Issue number4
Publication statusPublished - 2009


  • Affected siblings
  • Ataxia-telangiectasia
  • Hyper-IgM
  • Modifier genes
  • Phenotypic variations

ASJC Scopus subject areas

  • Hematology


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