GNE was first reported in relation to hereditary isolated macrothrombocytopenia in 2018 (Revel-Vilk et al, PMID: 30171045; Futterer et al, PMID: 29941673). Evidence supporting this gene-disease curation includes case-level data, segregation data, and experimental data. Twelve unique variants (missense, nonsense, frameshift) have been reported in humans. Variants in this gene have been reported in at least 10 probands in 7 publications. Variants in this gene segregated with disease in 8 additional family members. The gene disease relationship is supported by biochemical function experiments (PMID: 30171045). Of note, this gene has also been implicated in both GNE myopathy and sialuria, which are considered distinct from this isolated macrothrombocytopena. In summary, there is moderate 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 gene-disease pair was originally evaluated by the HT GCEP on 08/29/2020. It was reevaluated on 05/25/2022. As a result of this reevaluation, the classification was upgraded to Moderate with the addition of new case-level evidence (PMIDs: 33217855, 33198675, 34858435, 33637881, 35052006).
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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