PIGO was first reported in relation to autosomal recessive complex neurodevelopmental disorder in 2012 (Krawitz et al., PMID: 22683086). At least 15 variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data (12 points). Variants in this gene have been reported in at least 7 probands in 4 publications (PMID: 24417746, 27177984, 22683086, 28337824). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is recessive loss of function (Krawitz et al., PMID: 22683086). Of note, hyperphosphatasia is not a defining feature of this condition, but rather a biochemical phenotype that is occasionally detected in affected individuals. In summary, PIGO is definitively associated with an autosomal recessive complex neurodevelopmental disorder . 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 Epilepsy Working Group on 07/20/21 (SOP Version 8).
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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