title: Hematologically important mutations: leukocyte adhesion deficiency (first update).
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, mutations are found in ITGB2, the gene that encodes the β subunit of the β(2) 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 Le(a) and Le(b) 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.
authors: Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Edith
authors: E
authors: van de Vijver
authors: Anne
authors: A
authors: Maddalena
authors: Özden
authors: Ö
authors: Sanal
authors: Steven M
authors: SM
authors: Holland
authors: Gulbu
authors: G
authors: Uzel
authors: Manisha
authors: M
authors: Madkaikar
authors: Martin
authors: M
authors: de Boer
authors: Karin
authors: K
authors: van Leeuwen
authors: M Yavuz
authors: MY
authors: Köker
authors: Nima
authors: N
authors: Parvaneh
authors: Alain
authors: A
authors: Fischer
authors: S K Alex
authors: SK
authors: Law
authors: Nigel
authors: N
authors: Klein
authors: F Ilhan
authors: FI
authors: Tezcan
authors: Ekrem
authors: E
authors: Unal
authors: Turkan
authors: T
authors: Patiroglu
authors: Bernd H
authors: BH
authors: Belohradsky
authors: Klaus
authors: K
authors: Schwartz
authors: Raz
authors: R
authors: Somech
authors: Taco W
authors: TW
authors: Kuijpers
authors: Dirk
authors: D
authors: Roos
mesh_terms: D018821:CD18 Antigens / Q000097:blood / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002675:Child, Preschool; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood / Q000145:classification / Q000235:genetics* / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000097:blood / Q000235:genetics*; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D018821:CD18 Antigens; C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; C426650:SLC35C1 protein, human