The relationship between BCKDHB and maple syrup urine disease (autosomal recessive) was evaluated using the ClinGen Clinical Validity Framework as of September, 2018. Variants in BCKDHB were first reported in humans with this disease as early as 1991 (Nobukuni et al., PMID 2022752). At least 15 variants ( missense, nonsense, frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and experimental data. Approximately 35% of maple syrup urine disease cases can be attributed to pathogenic variants in BCKDHB (Strauss et al., 2006, PMID 20301495). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is supported by biochemical and in vitro assays. In summary, BCKDHB 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.
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).
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