ZMYM5 and Intellectual Disability

Evidence for an association between ZMYM5 and intellectual disability comes primarily from large‐scale genomic studies assessing a broad panel of candidate genes. In one multi‑patient study of 337 individuals with intellectual disability, ZMYM5 was among the candidate genes with identified de novo or recessive variants (PMID:27431290).

The genetic evidence is limited, with only a single variant event in an unrelated proband identified for ZMYM5. There is no extensive segregation analysis available, and the reported variant lacks replication in independent cohorts (PMID:27431290).

Inheritance in the current study was predominantly autosomal recessive, a pattern consistent with many of the candidate genes implicated in intellectual disability. Although ZMYM5 is included among these candidates, segregation data are minimal with no additional affected relatives confirmed to co‐segregate the variant.

Functional evidence for ZMYM5 is sparse and derived from early gene cloning and expression analysis studies. A functional assessment study reported the cloning of ZMYM5 (formerly designated ZNF237) and characterized its alternative splicing and expression patterns; however, no experiments directly link these observations to a pathogenic mechanism in intellectual disability (PMID:10894931).

Taken together, the genetic and functional data provide limited evidence that ZMYM5 contributes to the etiology of intellectual disability. The current data do not include robust segregation or recurrent variant evidence, and the functional studies are mainly descriptive rather than mechanistic.

Additional research including replication cohorts, detailed variant interpretation, and functional analyses are required to firmly establish the clinical validity of ZMYM5 in intellectual disability.

Key Take‑home: Although initial findings nominate ZMYM5 as a candidate gene in intellectual disability, further comprehensive studies are needed to solidify its role in clinical diagnostics.

References

• Molecular Psychiatry • 2017 • Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield PMID:27431290
• Cytogenetics and Cell Genetics • 2000 • Cloning of ZNF237, a novel member of the MYM gene family that maps to human chromosome 13q11-->q12 PMID:10894931

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