The USH1C gene has been associated with ARNSHL in at least 5 probands in 5 publications. 5 unique variants (missense, frameshift, large deletion) have been reported in humans, and variants in this gene segregated with disease in 5 additional family members (PMID: 12107438, 9653658). However, several variants were not scored due to lack of evidence for pathogenicity (PMID: 12136232). USH1C was first associated with this disease in humans in 1998 (Jain et al.). This gene-disease association is supported by 2 mouse models with deletions in the USH1C gene who were deaf but lacked the retinal phenotype of Usher Syndrome I as well as 1 expression study which showed that the longer transcript including the PDZ domain (which is thought to be the region affected to cause NSHL) was only expressed in the ear and not the retina. However, the mouse model from Williams 2009 was not scored because Johnson 2003 found that the mice displayed retinal degeneration at 9 months in addition to circling behavior (PMID: 19324851, 14519688). In summary, there is limited evidence to support this gene-disease association. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association.
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.