Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl

We report on an 11-year-old Japanese girl with combined immunodeficiency an d chromosomal instability. She had postnatal growth deficiency and microcep haly, preaxial polydactyly of the left hand, and susceptibility to infectio ns, Immunological studies showed marked lymphocytopenia (around 500/mul), r educed lymphocyte response to various mitogens, and reduced or absent serum IgA, IgG, and IgM. Cell biological studies of her primary skin fibroblasts demonstrated spontaneous chromosome aberrations and radiation hypersensiti vity. The combination of immunodeficiency, chromosomal instability, and rad iation hypersensitivity as seen in the girl is present in both ataxia-telan giectasia and Nijmegen breakage syndrome. Ataxia-telangiectasia was exclude d because of differences in clinical features and laboratory data. Likewise , Nijmegen breakage syndrome is unlikely to be the case because the charact eristic face, hyperpigmented spots, and mental retardation present in the s yndrome were missing in the girl, Sequence analysis of a Nijmegen breakage syndrome responsible gene, NBS1, revealed no mutations, A normal NBS1 produ ct was also demonstrated by immunoblot analysis using an anti-NBS1 antibody . We propose that the disorder in the girl represents a new combination of combined immunodeficiency and chromosomal instability. (C) 2001 Wiley-Liss, Inc.