Hematologically important mutations: leukocyte adhesion deficiency (first update)

Blood Cells Mol Dis. 2012 Jan 15;48(1):53-61. doi: 10.1016/j.bcmd.2011.10.004. Epub 2011 Nov 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CD18 Antigens / blood
  • CD18 Antigens / genetics*
  • Cell Adhesion / genetics
  • Child, Preschool
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism
  • Humans
  • Infant, Newborn
  • Leukocyte-Adhesion Deficiency Syndrome / blood
  • Leukocyte-Adhesion Deficiency Syndrome / classification
  • Leukocyte-Adhesion Deficiency Syndrome / genetics*
  • Leukocyte-Adhesion Deficiency Syndrome / immunology
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Membrane Proteins / blood
  • Membrane Proteins / genetics*
  • Monosaccharide Transport Proteins / blood
  • Monosaccharide Transport Proteins / genetics*
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Protein Conformation

Substances

  • CD18 Antigens
  • FERMT3 protein, human
  • Membrane Proteins
  • Monosaccharide Transport Proteins
  • Neoplasm Proteins
  • SLC35C1 protein, human