The clinical spectrum of leukocyte adhesion deficiency (LAD) III due to defective CalDAG-GEF1.
BACKGROUND
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.


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.


CONCLUSIONS
The hallmarks of the syndrome are recurrent infections accompanied by severe bleeding episodes distinguished by osteopetrosis like bone abnormalities and neurodevelopmental defects.
Kilic
Sara S
SS
Department of Pediatric Immunology, Uludag University School of Medicine, Bursa, Turkey.
Etzioni
Amos
A
D001842:Bone and Bones / Q000002:abnormalities / Q000000981:diagnostic imaging; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D011859:Radiography
D020662:Guanine Nucleotide Exchange Factors; C415483:RASGRP2 protein, human