title: Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan.
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.
authors.affiliation: 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. tmorio.ped@tmd.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.affiliation: 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.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Watanabe
authors.affiliation: 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.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Honda
authors.affiliation: 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.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: 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.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Imadome
authors.affiliation: Department of Pediatrics, Toyama University School of Medicine, Toyama, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Kotoka
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gatti
authors.affiliation: 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.
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D000293:Adolescent; D000328:Adult; D001260:Ataxia Telangiectasia / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007564:Japan; D008297:Male; D010641:Phenotype; D012189:Retrospective Studies; D035781:Siblings; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D007075:Immunoglobulin M
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