Mouse anti-Human URP2 polyclonal antibody

Neutrophilic granulocytes constitute the body's first line of defence against bacterial and fungal pathogens and orchestrate the inflammatory response. The analysis of monogenic defects of neutrophilic granulocytes has yielded important insights into mechanisms of the innate immune system. Severe congenital neutropenia is defined by decreased numbers of absolute neutrophil counts and may be caused by mutations in ELANE/ELA2, HAX1, GFI1, WASP or G6PC3. Qualitative defects of neutrophilic granulocytes affect migration, activation and bacterial killing capacity which are manifested clinically as leukocyte adhesion deficiencies I-III (ITGB2, SLC35C1, FERMT3) and chronic granulomatous disease (CYBB, NCF1, NCF2, CYBA).

Leukocyte adhesion deficiency-III (LAD3) is an extremely rare primary immunodeficiency disorder, transmitted with autosomal-recessive inheritance. It is caused by genetic alteration in the FERMT3 gene, which leads to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of integrin activation. LAD3 has features like bleeding syndrome of Glanzmann-type and leukocyte adhesion deficiency. FERMT3 mutation(s) have not been well characterized in Pakistani patients with LAD3. In this study, an infant and his family of Pakistani origin, presenting with clinical features of LAD, were investigated to determine the underlying genetic defect. Targeted next generation sequencing (TGS) and Sanger sequencing were performed to identify and confirm the causative mutations, respectively, and their segregation within the family. A novel, homozygous FERMT3 nonsense mutation (c.286C > T, p.Q96*) was found in the proband, and its co-segregation with LAD3 phenotype within the family was consistent with an autosomal recessive inheritance. Both parents were carriers of the same mutation. This family was offered prenatal diagnosis during first trimester of the subsequent pregnancy; the fetus carried the variant. In conclusion, our study is the first report to identify the novel homozygous variant c.286C > T, p.Q96*in the FERMT3 gene, which might be the causative mutation for LAD3 patients of Pakistani origin.