INTEGRIN BETA2 GENE VARIANT CAUSING LEUKOCYTE ADHESION DEFICIENCY TYPE 1 IN A PAKISTANI FAMILY

Background: Leukocyte adhesion deficiency type 1 (LAD1), an autosomal recessive condition, arises from partial or complete deficiency of CD18 expression. LAD1 patients commonly manifest recurrent skin and respiratory tract infections, delayed umbilical cord separation, and impaired wound healing due to hindered leukocyte migration. This study aims to clinically and molecularly diagnose LAD in a highly consanguineous Pakistani family, investigating a recurrent mutation within the integrin ?2 (ITGB2) gene. Methods: A comprehensive clinical and molecular diagnosis of LAD1 was made in on a patient from a consanguineous Pakistani family. Lymphocyte subset analysis was performed using a flow cytometer, followed by whole exome sequencing and DNA Sanger sequencing to identify the pathogenic mutation within the ITGB2 gene. Further to provide genetic counselling all the healthy siblings were also Sanger sequenced. Results: Flow cytometry indicated CD18 deficiency, while sequencing of the ITGB2 gene unveiled a nonsense mutation, c.186C>A, p. (Cys62*), located in exon four. This mutation segregates in an autosomal recessive pattern within the family. Conclusion: A mutation c.186C>A (Cys62*) in a patient of LAD1 was identified which is potentially pathogenic in nature. Pak J Physiol 2024;20(1):15-8