Hematologically important mutations: Leukocyte adhesion deficiency (second update)

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Roos D., Van Leeuwen K., Madkaikar M., Kambli P. M., Gupta M., Mathews V., ...More

BLOOD CELLS MOLECULES AND DISEASES, vol.99, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 99
  • Publication Date: 2023
  • Doi Number: 10.1016/j.bcmd.2023.102726
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE
  • Keywords: FERMT3, GDP-fucose transporter, ITGB2, Kindlin-3, LAD-I, LAD-II, LAD-III, SLC35C1, β2 integrins
  • Erciyes University Affiliated: Yes


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 beta subunit (CD18) of the beta(2) 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 Le(a) and Le(b) blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed beta 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 beta integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD.