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This summary evaluates the association between ZNF827 (HGNC:27193) and Sotos syndrome (MONDO_0019349) based on a recently published case report and exome sequencing analysis. In the reported study, a 2‑year‑old boy diagnosed with Sotos syndrome, accompanied by Hirschsprung disease, underwent both targeted and whole‑exome sequencing. Although the primary diagnostic mutations for Sotos syndrome were identified in another gene (NDS1), the exome sequencing analysis revealed that ZNF827 ranked among three genes overlapping with a previous genome‑wide association study for Hirschsprung disease (PMID:28399120). This observation suggests a potential but preliminary genetic link between ZNF827 and the Sotos syndrome phenotype, even though no specific ZNF827 variant meeting strict HGVS criteria was provided. The evidence is further limited by the lack of detailed segregation data and additional independent probands. The reported case therefore represents an initial insight that merits further investigation before ZNF827 can be confidently established as a causative gene for Sotos syndrome.
The functional mechanisms underlying a possible pathogenesis involving ZNF827 remain undefined as no experimental assays or animal/cellular models were presented. Consequently, both the genetic and experimental evidence supporting this association are currently limited. While the exome sequencing findings resonate with prior GWAS results for Hirschsprung disease, no in vitro or in vivo validation for ZNF827 was pursued in the study. Overall, the combined genetic and preliminary functional suggestion provides a basis for future research and underscores the critical need for additional studies to elucidate the contribution of ZNF827 to the Sotos syndrome spectrum. This association, though promising, should currently be considered for its potential clinical utility only in the context of further confirmatory evidence.
Gene–Disease AssociationLimitedAssociation based on a single proband with exome sequencing evidence identifying ZNF827 among candidate genes (PMID:28399120); lack of segregation data and additional probands constrains the overall evidence. Genetic EvidenceLimitedNo validated or HGVS‐compliant variant for ZNF827 was reported; genetic implication is inferred solely from its overlap with prior GWAS signals in one case. Functional EvidenceLimitedNo functional assays, model systems, or rescue experiments were provided to support a mechanistic role for ZNF827 in Sotos syndrome. |