Submitted April 3, 2008
Accepted May 28, 2008
Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome
Taizo Wada*, Masahiro Yasui, Tomoko Toma, Yuko Nakayama, Mika Nishida, Masaki Shimizu, Michiko Okajima, Yoshihito Kasahara, Shoichi Koizumi, Masami Inoue, Keisei Kawa, and Akihiro Yachie
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan
Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan
* Corresponding author; email: taizo{at}ped.m.kanazawa-u.ac.jp.
X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (
c) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual c expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.
