CHN1 was first reported in relation to autosomal dominant Duane retraction syndrome 2 in 2008 (Miyake et al., PMID:18653847). Duane retraction syndrome 2 is a congenital disorder characterized by restricted horizontal eye movement with globe retraction and palpebral fissure narrowing on attempted adduction. 12 missense variants that have been reported in 13 probands in 5 publications (PMIDs: 18653847, 21555619, 21715346, 29031989, 33004823) are included in this curation. The mechanism of pathogenicity has been reported to be gain of function. This gene-disease relationship is also supported by an animal model (PMID: 28346224). In summary, there is moderate evidence supporting the relationship between CHN1 and Duane retraction syndrome 2. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Brain Malformations GCEP on the meeting date December July 26, 2022 (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.