The Clinical Spectrum of Leukocyte Adhesion Deficiency (LAD) III due to Defective CalDAG-GEF1
- 213 Downloads
Leukocyte adhesion deficiency (LAD) type III is a rare syndrome characterized by severe recurrent infections, leukocytosis, and increased bleeding tendency. All integrins are normally expressed yet a defect in their activation leads to the observed clinical manifestations.
Materials and Methods
Less than 20 patients have been reported world wide and the primary genetic defect was identified in some of them. Here we describe the clinical features of patients in whom a mutation in the calcium and diacylglycerol-regulated guanine nucleotide exchange factor 1 (CalDAG GEF1) was found and compare them to other cases of LAD III and to animal models harboring a mutation in the CalDAG GEF1 gene.
The hallmarks of the syndrome are recurrent infections accompanied by severe bleeding episodes distinguished by osteopetrosis like bone abnormalities and neurodevelopmental defects.
KeywordsLeukocytes platelets integrins adhesion infections bleeding immunodeficiency
- 1.Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesions defects. In: Smith EM, Puck J, Ochs HD eds. Primary Immune deficiency disease. A molecular and genetic approach, 2nd ed. Oxford University Press; 2007. p. 550–64.Google Scholar
- 8.Alon R, Aker M, Feigelson S, Sokolowsky-Eisenberg M, Stauton D, Cinamon G, et al. A novel genetic leukocyte adhesion deficiency in sub-second triggering of integrin avidity by endothelial chemokines results in impaired leukocyte arrest on vascular endothelium under shear flow. Blood 2003;101:4437–45.PubMedCrossRefGoogle Scholar