Identification of a novel IGBP1 L49F variant in X‑linked intellectual disability

Following the initial report linking immunoglobulin-binding protein 1 ( IGBP1 , OMIM 300139) mutations to X-linked intellectual disability (XLID), we identified a novel IGBP1 missense variant (c.145C>T, p.L49F) in an affected proband. The patient manifests with intellectual disability, global developmental delay, and corpus callosum hypoplasia, which are consistent with the phenotypes previously recorded in OMIM 300139. Functional assays reveal that IGBP1 L49F variant alters its binding with protein phosphatase 2A catalytic subunit alpha (PP2Ac) and calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα), disrupting CaMKIIα phosphorylation homeostasis. Our findings suggest that the IGBP1 L49F variant is a plausible genetic candidate for the XLID phenotype observed in this patient.