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 immune system 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. The identification of SP110 mutations holds promise for accelerating the diagnosis and treatment of VODI syndrome, by providing a comprehensive panel for diagnosis and potentially leading to targeted therapies. In this case study, we examined a three-year-old girl born to a consanguineous union who was suspected of having an immunodeficiency disorder. Whole-exome sequencing (WES) and clinical assessments were conducted to screen for and confirm potentially pathogenic mutations. The detected mutation was further analyzed using bioinformatics tools to forecast its 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 identified a novel deletion-insertion mutation as a potential contributor to VODI syndrome by affecting the functionality of the SP110 protein. By including various mutations associated with the SP110 gene, this study aimed to expedite diagnosis by creating a comprehensive panel for VODI syndrome.