IRF2BPL Is Associated with Neurological Phenotypes.

摘要: Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family transcriptional regulators. Currently biological function this gene is obscure, and has not been associated with Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL are affected neurological symptoms. Five nonsense resulting premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, lack coordination. Two additional individuals, both missense variants, global developmental delay seizures relatively milder phenotype than those alleles. The bioinformatics signature based on population genomics consistent that intolerant to variation. We show fruit-fly ortholog, called pits (protein interacting Ttk69 Sin3A), broadly detected, including nervous system. Complete loss lethal early development, whereas partial knockdown RNA interference neurons leads neurodegeneration, revealing requirement for proper neuronal maintenance. identified behave as loss-of-function alleles model organism, ectopic expression range phenotypes. Taken together, our results required system humans flies, their phenotypes species.