OCM and Autism

In a recently reported case, oncomodulin (OCM) was implicated in autism through the detection of a 1.3 Mb microduplication at 7p22.1 in a 29‑month‑old male patient. This microduplication, identified via whole genome SNP microarray, encompassed 14 OMIM‐annotated genes, including OCM, and was associated with clinical features such as brachycephaly, protruding ear, delayed speech and language development, reduced eye contact, and cryptorchidism (PMID:25893121). While these findings suggest a potential association between the duplication and the autistic phenotype, the involvement of several genes in the duplicated interval limits the ability to attribute the phenotype solely to OCM. Moreover, there is an absence of segregation data or multiple unrelated probands that would otherwise strengthen a gene‐specific association. In light of this, the genetic evidence remains sparse and is categorized as Limited based on current ClinGen guidelines. This preliminary evidence highlights the need for future studies to isolate OCM variants and assess their individual contributions to autism.

Functional assessments of OCM provide complementary, biologically plausible data. Two independent experimental studies have interrogated the biochemical impact of specific site‐directed mutations in OCM. In particular, one study demonstrated that a variant described as c.164C>A (p.Ser55Asp) alters Ca2+ binding affinity and thermal stability of the protein, while another confirmed that modifications in the oncomodulin ion‑binding domains significantly influence metal ion coordination (PMID:2387865; PMID:8639547). These functional perturbations support a mechanism whereby altered ion binding may contribute to neurodevelopmental abnormalities, consistent with autism pathology. However, despite the integrity of these functional experiments, the absence of robust gene‐specific genetic evidence means that the overall gene‑disease association is not definitively established. Key take‑home: While functional studies reinforce the potential role of OCM in autism, the clinical utility remains limited until additional genetic confirmation is obtained.

References

• Case reports in genetics • 2015 • Case of 7p22.1 Microduplication Detected by Whole Genome Microarray in Workup of Child Diagnosed with Autism PMID:25893121
• The Journal of biological chemistry • 1990 • Site‑specific replacement of amino acid residues within the CD binding loop of rat oncomodulin PMID:2387865
• Biochemistry • 1996 • Introduction of a fifth carboxylate ligand heightens the affinity of the oncomodulin CD and EF sites for Ca2+ PMID:8639547

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