OMIM_backup@xiajingbo:165215-3-MECOM JSONTXT

In an 8-year-old Japanese boy (TRS3) with radioulnar synostosis and amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738), originally reported by Yoshida et al. (2010), Niihori et al. (2015) identified heterozygosity for a c.2248C-T transition (c.2248C-T, NM_001105078) in the MECOM gene, resulting in an arg750-to-trp (R750W) 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 his unaffected mother, in 382 ethnically matched controls, or in the dbSNP, 1000 Genomes Project, Human Genetic Variation, or ExAC databases. DNA from the father was not available. Chromatin immunoprecipitation-qPCR assays showed a significant reduction in immunoprecipitated DNA with the R750W 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 R750W 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 R750W mutant might represent a gain-of-function effect for AP1 and partial loss of function for TGF-beta (190180) signaling.