Hematologically important mutations : leukocyte adhesion deficiency (first update)

• Main Authors: Holland, Steven M., Belohradsky, Bernd H., Kuijpers, Taco W., Van de Vijver, Edith, Maddalena, Anne, Sanal, Özden, Uzel, Gulbu, Madkaikar, Manisha, de Boer, Martin, Van Leeuwen, Karin, Köker, M. Yavuz, Parvaneh, Nima, Fischer, Alain, Law, S. K. Alex, Klein, Nigel, Tezcan, F. Ilhan, Unal, Ekrem, Patiroglu, Turkan, Schwartz, Klaus, Somech, Raz, Roos, Dirk
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2013
• Online Access: https://hdl.handle.net/10356/99059; http://hdl.handle.net/10220/12687
• Institution: Nanyang Technological University

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, mutations are found in ITGB2, the gene that encodes the β subunit of the β2 integrins. This syndrome is characterized directly after birth by delayed separation of the umbilical cord. 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 (also called LAD-I/variant) 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 that is involved in the regulation of β integrin conformation.