Whole genome sequencing identifies novel structural variant in a large Indian family affected with X-linked agammaglobulinemia

X—linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in the BTK gene, characterized failure of development and maturation B lymphocytes. The estimated prevalence worldwide 1 190,000 male births. Recently, genome sequencing has been widely used difficult to diagnose familial cases. We report large Indian family suffering from XLA with five affected individuals. performed complete blood count, immunoglobulin assay, lymphocyte subset analysis for all patients analyzed Btk expression one patient his mother. Whole exome (WES) four patients, whole (WGS) two have performed. Carrier screening was done 17 members using Multiplex Ligation-dependent Probe Amplification (MLPA) haplotype ancestry mapping fineSTRUCTURE All had hypogammaglobulinemia low CD19+ cells. One who underwent estimation mother showed mosaic pattern. could not identify any single nucleotide variants or small insertion/ deletions WES dataset that correlates clinical feature patient. Structural variant through WGS data identifies novel deletion 5,296 bp at loci chrX:100,624,323–100,629,619 encompassing exons 3–5 gene. Family revealed seven carriers deletion. Two successful HSCT. Haplotype South Asian ancestry. led identification accurate genetic mutation which help early diagnosis leading improved outcomes, prevention permanent organ damage quality life, as well enabling counselling prenatal family.