MAMDC2 – Intellectual Disability

This review examines the association between MAMDC2 (HGNC:23673) and intellectual disability (MONDO_0001071). The primary evidence comes from multi‑patient genomic studies in which MAMDC2 was flagged as a candidate gene in a cohort largely characterized by autosomal recessive inheritance (PMID:27431290). However, the published reports did not detail any specific, validated variants in MAMDC2, nor did they provide in‐depth segregation data. Consequently, while its appearance in these high‐throughput analyses is noteworthy, the genetic evidence remains minimal.

The functional support for MAMDC2’s role in intellectual disability is also limited. Although MAMDC2 appears in the context of functional assessment studies of neurodevelopmental disorders, no direct experimental assays—such as expression studies or rescue models—were performed to evaluate its pathogenicity in intellectual disability. Further rigorous investigation, including comprehensive segregation analyses and targeted functional assays, is needed to clarify its clinical utility. Key take‑home: Initial genomic findings suggest a potential role for MAMDC2 in intellectual disability, but its use as a diagnostic marker requires further validation.

References

• Molecular Psychiatry • 2017 • Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield PMID:27431290
• Molecular Neurobiology • 2018 • Identification of De Novo DNMT3A Mutations That Cause West Syndrome by Using Whole-Exome Sequencing PMID:28386848

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