CECR2 and Cat‑Eye Syndrome

The association between CECR2 (HGNC:1840) and cat‑eye syndrome (MONDO:0007276) is supported by limited clinical evidence. A case report described a de novo small supernumerary marker chromosome (sSMC) in a girl with cat‑eye syndrome that encompassed the CECR2 region, although the expected ocular feature (coloboma) was absent (PMID:23112755). In a multi‑patient study, 27 cases with genomic gains in the proximal 22q11.1‑q11.21 region were analyzed, and the candidate gene list included CECR2 among others, indicating its potential involvement in the syndrome’s phenotypic spectrum (PMID:39402511).

Genetic evidence for the association is derived from these reports, cumulatively involving approximately 28 probands (PMID:23112755) (PMID:39402511). Inheritance appears to be autosomal dominant, as these chromosomal gains generally arise in a de novo manner, and no significant segregation among affected relatives was reported. One reported coding alteration, c.2590G>C (p.Gly864Arg), was identified in a functional assessment study; however, it was characterized in the context of neural tube defect research rather than cat‑eye syndrome specifically.

Functional experimental evidence shows that CECR2 plays an important role in chromatin remodeling and neural development, as demonstrated in murine models where its disruption leads to neurulation defects (PMID:15640247) (PMID:37424722). Despite this, no direct functional studies have been performed to delineate the molecular mechanism of CECR2 in cat‑eye syndrome, limiting the experimental underpinning for the gene‑disease association.

There is a degree of conceptual conflict as the case report noted the lack of a key eye phenotype (coloboma) despite the amplification of CECR2, which is considered a candidate for ocular features. This discrepancy, along with the presence of multiple candidate genes in the critical region, tempers the strength of the evidence linking CECR2 specifically to cat‑eye syndrome.

Integrating both the clinical and experimental findings, the available evidence suggests that while CECR2 is a plausible candidate gene within the duplicated region associated with cat‑eye syndrome, the data are insufficient to confidently establish a causative relationship. Additional targeted genetic and functional studies are required to elucidate the precise contribution of CECR2 to the disease phenotype.

Key take‑home: Although current evidence implicates CECR2 in the context of chromosomal duplications observed in cat‑eye syndrome, clinicians should exercise caution and consider the overall genomic context during diagnostic decision‑making.

References

• Molecular syndromology • 2012 • A de novo sSMC(22) Characterized by High‑Resolution Arrays in a Girl with Cat‑Eye Syndrome without Coloboma PMID:23112755
• Unknown Journal • Unknown Year • Multi‑patient analysis of cat‑eye syndrome cases with proximal 22q duplications PMID:39402511
• Human molecular genetics • 2005 • CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L PMID:15640247
• Frontiers in genetics • 2023 • Double whammy: the genetic variants in CECR2 and high Hcy on the development of neural tube defects PMID:37424722

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