Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1.
Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18+ cells revealed them to be derived from a single CD8+ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.
Tone
Yumi
Y
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Japan.
Wada
Taizo
T
Shibata
Fumie
F
Toma
Tomoko
T
Hashida
Yoko
Y
Kasahara
Yoshihito
Y
Koizumi
Shoichi
S
Yachie
Akihiro
A
D018821:CD18 Antigens / Q000032:analysis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics*; D009030:Mosaicism
D018821:CD18 Antigens