Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome.

Abstract

X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (gammac) 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 gammac 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.

• Authors: Taizo Wada, Masahiro Yasui, Tomoko Toma, Yuko Nakayama, Mika Nishida, Masaki Shimizu, Michiko Okajima, Yoshihito Kasahara, Shoichi Koizumi, Masami Inoue, Keisei Kawa, Akihiro Yachie
• Journal: Blood (Blood) Vol. 112 Issue 5 Pg. 1872-5 (Sep 01 2008) ISSN: 1528-0020 [Electronic] United States
• PMID: 18559672 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL2RG protein, human
• Interleukin Receptor Common gamma Subunit
• RNA Splice Sites

Topics

• Amino Acid Sequence
• Base Sequence
• DNA Mutational Analysis
• Diagnosis, Differential
• Humans
• Immunologic Deficiency Syndromes (diagnosis)
• Infant
• Interleukin Receptor Common gamma Subunit (genetics)
• Killer Cells, Natural (immunology, pathology)
• Male
• Mutation
• Phenotype
• RNA Splice Sites
• Skin (immunology, pathology)
• T-Lymphocytes (immunology, pathology)
• X-Linked Combined Immunodeficiency Diseases (diagnosis, genetics, immunology, pathology)