GREM2 was reported in connection with autosomal dominant tooth agenesis selective 9 in 2015 (Kantaputra et al., 2015 PMID: 26416033). Patients with condition present with dental anomalies such as isolated tooth agenesis, microdontia, short tooth roots and, taurodontism. Additional clinical features include sparse and slow-growing hair, and dry and itchy skin. 3 missense variants from 2 publications have been included in this curation (PMIDs: 26416033, 28992378). The mechanism of pathogenicity is unclear. One mutation generates a hypermorphic allele with an increased inhibitory activity while the impact of other mutations must be further investigated. This gene-disease pair is also supported by expression studies, protein interaction assays, and a mouse model (PMIDs: 24686385, 26416033, 19073177, 15039429). 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 Craniofacial Malformations Gene Curation Expert Panel on the meeting date 01/16/2025 (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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