Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1

Abstract

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. (Blood.

A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

“…Mosaicism due to somatic gene reversion has been observed in the immune system as well as in various other disease entities. [1][2][3][4][5][6]17,[35][36][37] Here we report a novel X-(S)CID family with a unique mutation in the extracellular part of CD132.…”

“…Reversed mutations have also been found in patients with Wiskott-Aldrich syndrome [15][16][17] and other primary T-cell immunodeficiencies such as those caused by mutations in CD3zeta, RAG-1, LAD and NEMO. 5,[18][19][20][21] The most common type of SCID in humans shows X-linked inheritance and is caused by mutations in the IL2RG gene. 22,23 This gene encodes an essential subunit, the common γ-chain (γ c , CD132), of a cytokine receptor subfamily that is essential for lymphocyte development, T-cell homeostasis, and peripheral immune responses.…”

Unprecedented diversity of genotypic revertants in lymphocytes of a patient with Wiskott-Aldrich syndrome

“…1 Reversion has been particularly prominent in severe immunodeficiency diseases, including Wiskott-Aldrich syndrome (WAS). [2][3][4][5][6][7][8][9][10] One common feature of most diseases for which reversion has been observed is a strong selective advantage for corrected cells in vivo. When characterized molecularly, revertant cells have exhibited only one or rarely a few revertant genotypes per patient.…”

Delayed Wound Healing in Leukocyte Adhesion Deficiency Type 1

“…3 He showed delayed wound healing after surgical excision of an infected urachal cyst from the age of 2 months …”