KEGG DISEASE: Leukocyte adhesion deficiency

DISEASE: Leukocyte adhesion deficiency

Entry

H00099                      Disease

Name

Leukocyte adhesion deficiency

Supergrp

Disorders of innate immunity [DS:H02525]
Primary immunodeficiency disease [DS:H01725]

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.

Category

Primary immunodeficiency

Brite

Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06546  IgSF CAM signaling
   H00099  Leukocyte adhesion deficiency
  nt06548  Integrin signaling
   H00099  Leukocyte adhesion deficiency

Pathway

hsa04670

Leukocyte transendothelial migration

hsa04517

IGSF CAM signaling

hsa04518

Integrin signaling

Network

nt06546 IgSF CAM signaling
nt06548 Integrin signaling

Gene

(LAD1) ITGB2 [HSA:3689] [KO:K06464]
(LAD2) SLC35C1 [HSA:55343] [KO:K15279]
(LAD3) FERMT3 [HSA:83706] [KO:K17084]

Other DBs

MeSH:

C535887 C535755 C567555

OMIM:

116920 266265 612840

Reference

PMID:17960151

Authors

Marodi L, Notarangelo LD.

Title

Immunological and genetic bases of new primary immunodeficiencies.

Journal

Nat Rev Immunol 7:851-61 (2007)
DOI:10.1038/nri2195

Reference

PMID:17162365

Authors

Kumar A, Teuber SS, Gershwin ME.

Title

Current perspectives on primary immunodeficiency diseases.

Journal

Clin Dev Immunol 13:223-59 (2006)
DOI:10.1080/17402520600800705

Reference

PMID:9737224

Authors

Ten RM.

Title

Primary immunodeficiencies.

Journal

Mayo Clin Proc 73:865-72 (1998)
DOI:10.4065/73.9.865

Reference

PMID:18424339

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)
DOI:10.1016/j.iac.2008.01.004

Reference

PMID:17952897

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)
DOI:10.1016/j.jaci.2007.08.053

Reference

PMID:19423742

Authors

Zimmerman GA

Title

LAD syndromes: FERMT3 kindles the signal.

Journal

Blood 113:4485-6 (2009)
DOI:10.1182/blood-2009-01-198853

Reference

PMID:1968911 (LAD1)

Authors

Arnaout MA, Dana N, Gupta SK, Tenen DG, Fathallah DM

Title

Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency.

Journal

J Clin Invest 85:977-81 (1990)
DOI:10.1172/JCI114529

Reference

PMID:11326280 (LAD2)

Authors

Lubke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Korner C

Title

Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency.

Journal

Nat Genet 28:73-6 (2001)
DOI:10.1038/88299

Reference

PMID:19234463 (LAD3)

Authors

Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, Moser M, Metin A, Fried M, Tomlinson I, Hogg N

Title

Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation.

Journal

Nat Med 15:306-12 (2009)
DOI:10.1038/nm.1931

» Japanese version

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Disease (3)   
   OMIM (3)   
All databases (3)   

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