SLC26A5 was first reported in relation to autosomal recessive nonsyndromic hearing loss (ARNSHL) in 2003 (Liu et al.; PMID: 12719379). Six variants (missense, nonsense, 5' UTR splicing) have been reported in four probands in four publications, however the association was only scored in one proband as other variants did not have sufficient evidence for pathogenicity (PMIDs: 24164807, 12719379, 17786286, 26969326). This gene-disease relationship has been studied in at least one case-control study at the aggregate variant level (PMID: 19492055). No statistically significant difference was found between patients and controls in the frequency of the identified variants. The mechanism for disease is reported to be loss of function (PMIDs: 24164807, 18466744, 12239568). This gene-disease association is also supported by mouse models, biochemical function studies, and expression studies (PMIDs: 12239568, 10821263, 11423665, 12719379, 18466744, 27091614, 17998209). There is strong evidence that loss of SLC26A5 causes hearing loss in mice, yet there is limited evidence in humans. Researchers have posited that humans have a compensatory mechanism that mice do not have (Hosoya et al. 2016; PMID: 27091614). Due to the lack of convincing human patients, the Hearing Loss Gene Curation Expert Panel classified this gene-disease relationship as Limited. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the Hearing Loss Gene Curation Expert Panel on 12/19/2017. It was reevaluated on 1/19/2022 (SOP v8). As a result of this reevaluation, the classification did not change.
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.