PTGS1 was first reported in relation to autosomal dominant platelet-type bleeding disorder 12 in 2018 (PMID: 28983057). So far, only two unique variants (one in-frame deletion and one missense) have been reported in humans. Recently, another PTGS1 missense variant (NM_000962:exon5:c.412T>C (p.W138R )) was identified in an affected mother and her affected son by an expert member of the Hemostasis/Thrombosis GCEP. Both individuals had normal platelet count and size and normal platelet surface glycoprotein expression. In addition, they presented with absent aggregation to AA and and reduced to low dose collagen with a normal response to endoperoxide analog suggesting a cyclooxygenase deficiency. This gene-disease relationship includes case-level data and experimental data. This gene-disease relationship is supported by protein expression A that the PTGS1 protein is preferentially expressed constitutively at high levels in selected cells, including endothelium, monocytes, platelets, renal collecting tubules, and seminal vesicles [PMID: 18657230], protein expression B that COX-1 variant showed hypo-glycosylated pattern [PMID: 33326144], functional alteration in non-patient cells that the PTGS1 N143S variant caused a dominant-negative effect of the COX-1 enzyme activity and reduced downstream TXB2 synthesis [PMID: 33326144]. In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
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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