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This report describes a child with polymicrogyria who presents with severe intellectual disability and microcephaly (PMID:36672848). Exome sequencing identified a de novo missense variant, c.747G>A (p.Met249Ile), in TUBG2 that is absent from control databases and predicted to be deleterious by multiple in silico tools (PMID:36672848). Functional assessments in patient-derived lymphoblasts and in transfected 293T cells showed a reduction in TUBG2 protein levels along with an increased interaction with GCP2, supporting a plausible pathogenic mechanism.
Although these findings are supported by robust functional data, the genetic evidence is currently derived from a single proband with no additional segregation data. This preliminary evidence assigns a limited gene‑disease association for TUBG2 in polymicrogyria. Key take‑home message: the integration of de novo genetic findings with supportive functional assays warrants further investigation into TUBG2 as a candidate gene for polymicrogyria and supports its consideration in diagnostic evaluation.
Gene–Disease AssociationLimitedEvidence is based on a single de novo variant detected in one proband with supportive functional assays demonstrating altered TUBG2 activity (PMID:36672848). Genetic EvidenceLimitedThe de novo missense variant c.747G>A (p.Met249Ile) was identified in a patient with polymicrogyria with no additional segregation data available (PMID:36672848). Functional EvidenceModerateFunctional assays in patient-derived cells and transfected models demonstrated decreased mutant protein levels and an increased interaction with GCP2, which is consistent with a pathogenic mechanism (PMID:36672848). |