Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease with a heterogeneous background. FCGR2C mutations were defined in one third of the patients but exact genetic players have not been fully elucidated yet. Although childhood ITP present as benign and self-limiting, ITP in adulthood is a chronic disease with treatment challenges. This study aimed to focus on adult ITP patients by using a whole genome genotyping that is a valuable approach to identify the responsible genomic regions for the disease phenotypes of complex disorders.
Methods: Herein 24 adult primary-refractory for ITP patients were evaluated using HumanCytoSNP- 12BeadChip, Illumina. Forty-six age and sex matched healthy individuals, and patients with non- hematological conditions were also analyzed as controls. Identified CNV regions were verified by qRT- PCR. T-cell receptor beta and delta (TCRB/TCRD) clonality were also assessed by heteroduplex analysis in mosaic cases.
Results: Several CNV losses and gains were defined (losses:2q,7q,17q,19p, and gains: 1q,2p,3q,4q,7q,10q,12p,13q,14q,15q,17p,20q,21p,22q,Xp). Mosaic structural changes of different sizes (0.2-17.77Mb) were identified in five patients and three of them showed TCRG/TCRD clonality. CNV regions that were unique to ITP patients were also identified for the first time and among these genes, those related to immune regulation, cellular trafficking, and cytoskeleton assembly were noteworthy.
Conclusion: Identified CNV regions harbor several candidate genes, the functions of which might shed light on the pathogenesis of chronic ITP