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In a recent report, a 2‑year‑old patient with Sotos syndrome and Hirschsprung disease underwent exome sequencing which identified variants in ZNF827, among others, that overlapped with previous HSCR GWAS signals (PMID:28399120). This observation comes from a combined analysis presented both as a single case and a multi‑patient study, representing the first tentative association of ZNF827 with Hirschsprung disease. The genetic evidence consists of the identification of ZNF827 in the sequencing data from one proband (PMID:28399120) without additional reported segregation or familial recurrence data.
Given the absence of extensive segregation analysis and functional experimental studies, the overall clinical validity of the association is currently rated as Limited. Although the overlap with prior GWAS data adds a suggestive layer of support, the lack of independent replication and functional corroboration limits the utility of this finding for immediate diagnostic decision‑making. Key take‑home: while the initial exome‑sequencing results hint at a possible role for ZNF827 in Hirschsprung disease, further studies are needed to establish the strength of this association for both clinical and commercial applications.
Gene–Disease AssociationLimitedBased on a single proband (PMID:28399120) with no extended segregation data, only a tentative association is inferred between ZNF827 and Hirschsprung disease. Genetic EvidenceLimitedThe identification of ZNF827 in exome sequencing with overlap from HSCR GWAS provides preliminary genetic support; however, the evidence is limited by the single report and lack of independent replication. Functional EvidenceLimitedNo functional studies or experimental models were provided to substantiate the mechanistic role of ZNF827 in Hirschsprung disease. |