OMIM_backup@xiajingbo:165215-2-MECOM JSONTXT

In an 8.75-year-old Japanese girl (TRS2) with radioulnar synostosis and amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738), originally described bySugita et al. (2007), Niihori et al. (2015) identified heterozygosity for a c.2252A-G transition (c.2252A-G, NM_001105078) in the MECOM gene, resulting in a his751-to-arg (H751R) substitution at a highly conserved residue within the eighth zinc finger motif in the C-terminal zinc finger domain. The mutation was not present in her unaffected parents, in 382 ethnically matched controls, or in the dbSNP, 1000 Genomes Project, Human Genetic Variation, or ExAC databases. Chromatin immunoprecipitation-qPCR assays showed a significant reduction in immunoprecipitated DNA with the H751R mutant compared to wildtype EVI1. Luciferase assays using pAP1 (165160)-luc in transfected NIH3T3 and HEK293 cells demonstrated enhanced suppression of relative luciferase activity with the H751R mutant compared to wildtype EVI1, whereas luciferase assays using a p3TP-lux vector showed an attenuated response with the mutant. Niihori et al. (2015) suggested that the H751R mutant might represent a gain-of-function effect for AP1 and partial loss of function for TGF-beta (190180) signaling.