Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome.
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.
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Japan. taizo@ped.m.kanazawa-u.ac.jp
Taizo
T
Wada
Masahiro
M
Yasui
Tomoko
T
Toma
Yuko
Y
Nakayama
Mika
M
Nishida
Masaki
M
Shimizu
Michiko
M
Okajima
Yoshihito
Y
Kasahara
Shoichi
S
Koizumi
Masami
M
Inoue
Keisei
K
Kawa
Akihiro
A
Yachie
D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis; D007223:Infant; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D009154:Mutation; D010641:Phenotype; D022821:RNA Splice Sites; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D022821:RNA Splice Sites