The relationship between QDPR and dihydropteridine reductase (DHPR) deficiency, an autosomal recessive disorder of tetrahydobiopterin regeneration, was evaluated using the ClinGen Clinical Validity Framework as of June 15th, 2018. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in QDPR were first reported in humans with this disease as early as 1998 (Furukawa et al, PMID 9667588). Fifteen unique variants (missense, frameshift, nonsense, intronic, and in frame duplication) were curated in 15 probands from 5 publications (Howells et al, 1990, PMID 2116088; Smooker et al, 1995, PMID 7783174; Ikeda et al, 1997, PMID 9341885; Romstad et al, 2000, PMID 11153907; Ye et al, 2008, PMID 19099731). More evidence is available in the literature but the maximum score for genetic evidence (12 points ) has been reached. The mechanism for disease is loss of function. This gene-disease relationship is supported by the function of DHPR, which is consistent with the disease process (PMIDs 14114862, 3033643), as well as the finding of hyperphenylalaninemia in a null mouse model (Xu et al, 2014, PMID 24240194). In summary, QDPR is definitively associated with DHPR deficiency. 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).
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.