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This summary evaluates the association between EPYC (HGNC:3053) and posterior amorphous corneal dystrophy, a rare autosomal dominant condition (MONDO_0013027). The disorder is clinically characterized by decreased corneal thickness, posterior lamellar opacification, and changes in corneal curvature. The association is based on evidence derived from copy number variants detected in patients presenting with these corneal abnormalities.
Two independent case reports provide the genetic evidence. In one study, a 7‐year‐old male with posterior amorphous corneal dystrophy was found to carry a 1.3 Mb interstitial deletion at 12q21.33 that encompassed EPYC along with other small leucine‑rich proteoglycan genes (PMID:30058938). A separate report described a Guatemalan family in which three affected members harbored a 0.304 Mb heterozygous deletion at the same locus (PMID:29671669). Both studies support the concept of a contiguous gene syndrome leading to a combined haploinsufficiency effect.
The genetic evidence is limited by the fact that the deletions affect multiple genes, making it difficult to isolate the contribution of EPYC relative to its neighboring genes. Neither study reported isolated EPYC coding variants that meet the criteria for a single‐gene association, and no specific HGVS coding variant for EPYC was provided.
Segregation analyses in the familial report demonstrated that the deletion cosegregated with the disease phenotype in additional affected relatives, supporting the role of this chromosomal region. However, the evidence remains constrained to copy number variants identified in a single proband and one small family, without further corroboration from larger patient cohorts.
Functional evidence directly linking EPYC to the pathogenesis of posterior amorphous corneal dystrophy is sparse. In the absence of independent functional assays or animal models solely for EPYC, the pathogenic mechanism is inferred from its inclusion in a contiguous deletion. No direct experimental validation has been provided that isolates EPYC’s functional contribution to the corneal phenotype.
In conclusion, while the available data from two independent case reports suggest that heterozygous deletions involving EPYC contribute to posterior amorphous corneal dystrophy, the evidence is limited by the inherent complexity of contiguous gene syndromes. The key take‑home message is that, despite supportive segregation and clinical consistency, the isolated role of EPYC remains uncertain and warrants further molecular and functional investigation for clinical diagnostic decision‑making.
Gene–Disease AssociationLimitedAssociation derives from two independent case reports (PMID:30058938, PMID:29671669) that identified heterozygous deletions encompassing EPYC in patients with PACD, indicating a combined haploinsufficiency effect within a contiguous gene syndrome. Genetic EvidenceLimitedGenetic evidence is based solely on copy number variant studies in one sporadic case and one family, lacking isolated EPYC variants. The data includes one proband and segregation observed in two additional affected relatives (PMID:30058938, PMID:29671669). Functional EvidenceLimitedNo direct functional studies specific to EPYC in the context of PACD have been reported; the pathogenic mechanism is inferred from its inclusion in a contiguous gene deletion rather than from independent experimental validation. |