The relationship between DBT and maple syrup urine disease (autosomal recessive) was evaluated using the ClinGen Clinical Validity Framework as of October, 2018. Variants in DBT were first reported in humans with the disease as early as 1991 (Herring et al., PMID: 1990841). At least 11 variants (missense, nonsense, frameshift, deletions) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. About 20% of MSUD cases are attributed to variants in this gene (Strauss et al., 2013; PMID: 20301495). More evidence is available in the literature, but the maximum score for genetic evidence and experimental evidence (18 pts.) has been reached. In summary, DBT is definitively associated with autosomal recessive maple syrup urine disease. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Aminoaciopathy Gene Curation Expert Panel on 10/30/18 (SOP Version 5).
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.