POLR1B was first reported in relation to autosomal dominant Treacher-Collins syndrome 4 in 2020 (Sanchez et al., PMID: 31649276). Treacher-Collins syndrome 4 is disorder of craniofacial development characterized by craniofacial dysmorphisms including downslanting palpebral fissures, malar and mandibular hypoplasia, and microtia. Most patients have conductive deafness with atretic external ear canals. Choanal atresia and cleft palate have also been observed. At least three missense variants have been reported in six probands in two publications. Though the points scored lead to a limited classification, the expert panel believes there is sufficient evidence to classify missense variants at the position p.Arg1003 as moderate. Evidence supporting this gene-disease relationship includes expression data and animal models (PMID: 31649276). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 2/16/2023. (SOP Version 9)
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).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.