P036: Estimating incidence and exploring phenotypic spectrum of X-linked disorders of purine metabolism in All of Us

Prior studies on HPRT1- and PRPS1-related disorders, both X-linked conditions, have utilized phenotypically ascertained cohorts to determine their prevalence, genotype-phenotype associations, and phenotypic spectrum. While informative, this ascertainment method introduces biases in interpreting the degree of phenotypic manifestations and variant pathogenicity, while also limiting investigation of pleiotropy. In this study, we adopted a genotype-first approach using a bioinformatics variant filtering pipeline and the All of Us EHR-linked population database to identify putative pathogenic variants in HPRT1 and PRPS1, estimate live birth incidence, and explore phenotypic associations.