KEGG   DISEASE: H00099Help
Entry
H00099                      Disease                                

Name
Leukocyte adhesion deficiency (LAD), including the following four diseases:
Leukocyte adhesion deficiency (I);
Leukocyte adhesion deficiency (II);
Leukocyte adhesion deficiency (III);
LAD with Rac2 deficiency
Description
Leukocyte adhesion deficiency (LAD) is a rare, autosomal recessive genetic disorder in which neutrophils fail to mobilize and migrate to sites of injury. At least three genetically distinct forms of this group of disorders have been described: LAD I, II, and III. Defects in the expression of beta2-integrins and fucose- containing proteins account for LAD-I and LAD-II, respectively. In LAD-III integrin expression by leukocytes is normal, but the integrins fail to generate high avidity for their cognate endothelial-cell ligands. Mutations in the KINDLIN3 (official symbol FERMT3), a gene that encodes an intracellular protein that interacts with cytoplasmic tails of beta-integrins in hematopoietic cells, is the cause of LAD-III. Dominant-negative mutations resulting in deficiency of ras-related C3 botulinum toxin substrate (Rac2), the predominant hematopoeitic-specific Rho GTPase in neutrophils also leads to leukocyte adhesion deficiency.
Category
Primary immunodeficiency
BRITE hierarchy
Pathway
Leukocyte transendothelial migration
Gene
ITGB2 [HSA:3689] [KO:K06464]
SLC35C1 [HSA:55343] [KO:K15279]
FERMT3 [HSA:83706] [KO:K17084]
RAC2 [HSA:5880] [KO:K07860]
Other DBs
Reference
PMID:17960151 (description, gene)
  Authors
Marodi L, Notarangelo LD.
  Title
Immunological and genetic bases of new primary immunodeficiencies.
  Journal
Nat Rev Immunol 7:851-61 (2007)
Reference
PMID:17162365 (gene)
  Authors
Kumar A, Teuber SS, Gershwin ME.
  Title
Current perspectives on primary immunodeficiency diseases.
  Journal
Clin Dev Immunol 13:223-59 (2006)
Reference
PMID:9737224 (gene)
  Authors
Ten RM.
  Title
Primary immunodeficiencies.
  Journal
Mayo Clin Proc 73:865-72 (1998)
Reference
PMID:18424339 (gene)
  Authors
Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.
  Title
Genetic diagnosis of primary immune deficiencies.
  Journal
Immunol Allergy Clin North Am 28:387-412, x (2008)
Reference
PMID:17952897 (gene)
  Authors
Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.
  Title
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
  Journal
J Allergy Clin Immunol 120:776-94 (2007)
Reference
PMID:19423742 (gene)
  Authors
Zimmerman GA
  Title
LAD syndromes: FERMT3 kindles the signal.
  Journal
Blood 113:4485-6 (2009)
Reference
  Authors
Ambruso DR, Knall C, Abell AN, Panepinto J, Kurkchubasche A, Thurman G, Gonzalez-Aller C, Hiester A, deBoer M, Harbeck RJ, Oyer R, Johnson GL, Roos D
  Title
Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2  mutation.
  Journal
Proc Natl Acad Sci U S A 97:4654-9 (2000)

» Japanese version

DBGET integrated database retrieval system