Uncovering Deletion/Insertion Mutations in Veno-Occlusive Disease with Immunodeficiency Syndrome in An Iranian Family: A Case Report

Abstract

Veno-occlusive disease with immunodeficiency (VODI) syndrome is a rare genetic disorder characterized by immunesystem irregularities and a significant mortality rate, despite its infrequency. SP110, situated on chromosome 2q37.1,plays a pivotal role in VODI syndrome, and its association with tuberculosis has been extensively studied. Theidentification of SP110 mutations holds promise for accelerating the diagnosis and treatment of VODI syndrome, byproviding a comprehensive panel for diagnosis and potentially leading to targeted therapies. In this case study, weexamined a three-year-old girl born to a consanguineous union who was suspected of having an immunodeficiencydisorder. Whole-exome sequencing (WES) and clinical assessments were conducted to screen for and confirmpotentially pathogenic mutations. The detected mutation was further analyzed using bioinformatics tools to forecastits impact on protein structure. WES analysis revealed a novel deletion-insertion mutation, c.1181-1182delAGinsT,within SP110. Protein analysis indicated substantial structural modifications in the SP110 protein. This study identifieda novel deletion-insertion mutation as a potential contributor to VODI syndrome by affecting the functionality of theSP110 protein. By including various mutations associated with the SP110 gene, this study aimed to expedite diagnosisby creating a comprehensive panel for VODI syndrome.

Keywords

• bioinformatics
• mutation
• sp110 protein
• whole-exome sequencing
• veno-occlusive disease with immunodeficiency syndrome