Sequence variants in the ITGB2 gene underlying leukocyte adhesion deficiency Type-1 in four consanguineous families

Abstract

Integrins are integral transmembrane proteins involved in various biological activities. One such protein β2 integrin CD18, encoded by ITGB2 gene, is involved in leukocyte adhesion and wound healing. Leukocyte adhesion and crawling being the key process in combating infections are mainly facilitated by β2 integrins. Sequence variants in the ITGB2 gene cause leukocyte adhesion deficiency, type I (LAD1). To search for the disease-causing sequence variants in four patients with LAD1 born to four different consanguineous parents of Pakistani origin. Flow cytometry was used to measure CD18 levels. Genomic DNA was extracted from the blood of the patients, parents, and healthy siblings. Using exon-specific primers, the ITGB2 gene was Sanger sequenced. Clinical features including skin abscesses, delayed umbilical cord separation, mild omphalitis, and neutrophilia were recorded in the patients. Flow-cytometric analysis revealed highly reduced CD18 levels (< 2 %) in the patients. Sequence analysis of the ITGB2 gene revealed four disease-causing variants, including two novels [p.(Tyr130*), p.(Ala245Pro)], and two previously reported [p. (Cys62*), p.(Asp128Tyr)]. Identification of the LAD1 causative variants further expanded the mutation spectrum in the ITGB2 gene. This study will facilitate genetic counseling of the families carrying LAD1 type features in the Pakistani population.