PIGM was first reported in relation to autosomal recessive hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency in 2006 (Almeida et al., PMID 16767100). Two variants (promoter, missense) that have been reported in 6 probands in 4 publications (PMIDs 16767100, 31445883, 39119839, 39425582) are included in this curation. Patients have a range of symptoms, including macrocephaly, hepatosplenomegaly, cytopenias, and portal vein thrombosis. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is also supported by in vitro and in vivo assays showing a deficiency in glycosylphosphatidylinositol (GPI) biosynthesis (PMIDs 11226175, 16767100). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on February 6th, 2025 (SOP Version 11).
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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