PYCR1 was first reported in relation to autosomal recessive cutis laxa in 2009 (Guernsey DL, et al., 2009, PMID: 19576563; Reversade B, et al., 2009, PMID: 19648921). At least 40 unique variants (e.g. missense, in-frame indel, nonsense, frameshift, etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 13 probands in the two initial publications. Variants in this gene segregated with disease in two additional family members (Guernsey DL, et al., 2009, PMID: 19576563). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by the function of PYCR1 in proline metabolism, its expression in bone and skin, and animal models in Xenopus and Zebrafish with partial recapitulation of disease. In summary, PYCR1 is definitively associated with autosomal recessive cutis laxa. 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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