CDCA5 – Cornelia de Lange Syndrome

A recent report described a 23‑year‑old male with a clinical presentation that overlaps with Cornelia de Lange syndrome, including intellectual disability, dysphagia, gastroesophageal reflux, abnormal skeletal features, and atypical behavior (PMID:26164757). In this case, a 1.6 Mb deletion at chromosome region 11q12.3‑11q13.1 was detected by chromosome microarray, and the deleted region encompassed several genes, including CDCA5. Although the deletion involves multiple genes, CDCA5 is of particular interest given its role in the cohesin pathway—a pathway already implicated in Cornelia de Lange syndrome.

The genetic evidence for an association between CDCA5 and Cornelia de Lange syndrome is limited. Only two probands have been described to date (PMID:26164757), and no detailed segregation data or independent mutational analysis for CDCA5 have been provided. Moreover, while the inheritance pattern for classic Cornelia de Lange syndrome is autosomal dominant, segregation analysis specific to CDCA5 is currently unavailable.

Genetic investigations in the reported case utilized precise deletion mapping; however, because the deletion spanned a number of genes, the contribution of CDCA5 remains speculative. The absence of additional independent CDCA5 mutations in other families or detailed functional studies in developmental models further limits the strength of genetic evidence.

Functional assessment studies have evaluated CDCA5 in contexts unrelated to Cornelia de Lange syndrome. For instance, studies in hepatocellular carcinoma and lung adenocarcinoma have demonstrated that CDCA5 is involved in cell cycle regulation and pre‑mRNA processing (PMID:32065447, PMID:34330897). These experimental data, although robust within oncological settings, do not clarify a mechanistic role for CDCA5 in the developmental anomalies characteristic of Cornelia de Lange syndrome.

In summary, the current evidence linking CDCA5 to Cornelia de Lange syndrome is limited by a small number of reported cases and the inherent complexity of multi‑gene deletions. Functional studies in other disease contexts provide insights into the cellular roles of CDCA5 but do not directly support its involvement in CdLS pathogenesis. Further research is required to establish whether CDCA5 independently contributes to the clinical phenotype.

Key Take‑home: While preliminary observations suggest CDCA5 may be implicated in CdLS‑like features, its utility as a diagnostic marker remains uncertain until additional, gene‑specific evidence is available.

References

• Gene • 2015 • Deletion of 11q12.3-11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome PMID:26164757
• Journal of Cellular Biochemistry • 2020 • STAT1‑induced upregulation of lncRNA RHPN1‑AS1 predicts a poor prognosis of hepatocellular carcinoma and contributes to tumor progression via the miR‑485/CDCA5 axis PMID:32065447
• Nature Communications • 2021 • AKT3‑mediated IWS1 phosphorylation promotes the proliferation of EGFR‑mutant lung adenocarcinomas through cell cycle‑regulated U2AF2 RNA splicing PMID:34330897

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