POR was first reported in relation to autosomal recessive POR-related Antley- Bixler Syndrome in 2004 (Flück et al., PMID: 14758361). Antley-Bixler Syndrome is a rare syndromic craniosynostosis characterized by midface hypoplasia, radiohumeral synostosis, femoral bowing, and joint contractures. Phenotypes specific to POR-related Antley-Bixler include steroidogenesis and genital anomalies. There is variation seen in the literature, with some cases with pathogenic POR variants having isolated craniofacial phenotypes or isolated genital anomalies and steroidogenesis. The cases included in this curation for POR and POR-related Antley-Bixler Syndrome exhibited both craniofacial phenotypes and genital anomalies/steroidogenesis. This curation includes 6 variants (missense, splice, nonsense, frameshift) have been reported in 7 probands from 6 publications (PMIDs: 32615689, 18853185, 32851239, 20124576, 26670660, 28841001). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease association is also supported by animal models and in vitro functional assays (PMIDs: 24086598, 15793702). In summary, POR is definitively associated with autosomal recessive POR-related Antley-Bixler Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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