Systems-Level Integration of Multi-Omics Identifies Genetic Modifiers of TANGO2 Deficiency Disorder.

ABSTRACT: TANGO2 deficiency disorder is a rare autosomal recessive disease (~100 cases reported worldwide). Despite being caused by loss-of-function variants in the TANGO2 gene, patients exhibit marked phenotypic variability, including intrafamilial differences among individuals carrying identical variants. To uncover potential modifier mechanisms influencing disease severity, we developed an integrative Systems biology framework, combining exome sequencing, transcriptomics, variant effect prediction, and Human Phenotype Ontology mapping. This approach was applied to two siblings carrying identical compound heterozygous TANGO2 variants but opposite clinical outcomes: one severely affected and one asymptomatic. Personalized protein-protein interaction networks and combined univariate an

SUBMITTER: Airoldi M 

PROVIDER: S-EPMC12730736 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature