MDM1 – Neurodevelopmental Disorder

A recent study (PMID:38868186) reported a de novo mutation in MDM1, identified as c.1197dupT (p.Lys400Ter), in a patient presenting with a spectrum of neurodevelopmental features including global developmental delay, seizure, hypothyroidism, and intellectual disability. The mutation was observed in a single proband, and the inheritance pattern is consistent with an autosomal dominant mechanism. Although there was no evidence of segregation beyond the de novo occurrence, the clinical presentation aligns with the neurodevelopmental disorder phenotype (MONDO_0700092). This limited genetic evidence suggests that the MDM1 mutation may contribute to disease pathogenesis, yet further cases and confirmatory studies are needed to strengthen this association.

While the study provided extensive functional analysis for the concomitant TLK1 variant, no specific experimental work was performed to evaluate the MDM1 mutation. As a result, the functional evidence specific to MDM1 remains limited. Despite this, the overall clinical context—including the de novo occurrence and the overlapping phenotypic features with established neurodevelopmental disorders—supports consideration of MDM1 in differential diagnosis. Additional functional studies and replication in further unrelated individuals will be essential to firmly establish the gene’s role in neurodevelopmental disorders. The integration of both genetic and preliminary functional insights provides an important basis for diagnostic decision-making and commercial assay development.

References

• iScience • 2024 • De novo TLK1 and MDM1 mutations in a patient with a neurodevelopmental disorder and immunodeficiency PMID:38868186

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