BTD and autosomal recessive Biotinidase Deficiency was reported in 1994 by Cole et al. (PMID: 7509806). Profound biotinidase deficiency is defined as less than 10% of mean normal serum enzyme activity; partial biotinidase deficiency is defined as between 10% and 30% of mean normal serumactivity (PMID: 26810761). Patients with Biotinidase deficiency are treated with biotin. At least 200 unique variants (missense, frameshift, nonsense etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data, including an animal model. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. In summary, BTD is definitively associated with autosomal recessive Biotinidase Deficiency. 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 Hearing Loss Gene Curation Expert Panel in collaboration with the ClinGen General Gene Curation Working Group on 9/25/19.
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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