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Hematologically Important Mutations: Leukocyte Adhesion Deficiency (Second Update) Publisher Pubmed



Roos D1 ; Van Leeuwen K1 ; Madkaikar M2 ; Kambli PM2 ; Gupta M2 ; Mathews V3 ; Rawat A4 ; Kuhns DB5 ; Holland SM6 ; De Boer M1 ; Kanegane H7 ; Parvaneh N8 ; Lorenz M9 ; Schwarz K9, 10 Show All Authors
Authors
  1. Roos D1
  2. Van Leeuwen K1
  3. Madkaikar M2
  4. Kambli PM2
  5. Gupta M2
  6. Mathews V3
  7. Rawat A4
  8. Kuhns DB5
  9. Holland SM6
  10. De Boer M1
  11. Kanegane H7
  12. Parvaneh N8
  13. Lorenz M9
  14. Schwarz K9, 10
  15. Klein C11
  16. Sherkat R12
  17. Jafari M12
  18. Wolach B13
  19. Den Dunnen JT14
  20. Kuijpers TW1, 15
  21. Koker MY16

Source: Blood Cells, Molecules, and Diseases Published:2023


Abstract

Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, characterized directly after birth by delayed separation of the umbilical cord, mutations are found in ITGB2, the gene that encodes the β subunit (CD18) of the β2 integrins. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Lea and Leb blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed β integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells, involved in the regulation of β integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD. © 2023