A MECOM variant in an African American child with radioulnar synostosis and thrombocytopenia

MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia

“…[6][7][8] However, most of our patients (as well as those in the IBMFS study by Bluteau et al 9 ) were not affected by RUS, including 2 patients bearing a mutation reported in the 3 patients with RUSAT2. 6,7,9 For a short time in embryonic development, the radius and ulna share a common perichondrium, and a perturbation of the process of segmentation by abnormal genetic or teratogenic factors can lead to a more or less distinct synostosis, 34 a fact which might explain the differences in the penetrance of this trait. MECOM is specifically expressed in the emerging limb buds in embryogenesis, but insufficient production seems to have no effect on bone development; skeletal abnormalities were not observed in any of the Evi1 knockout models.…”

“…Recently, 2 other families with RUSAT2 were described. 7,8 A study investigating germ line mutations in a group of 179 patients with IBMFS identified 6 more patients with MECOM mutations; interestingly, only 1 of them had RUS (supplemental Table 1). 9 In this study, we report on 12 patients with yet unclassified AT from different families caused by mutations in MECOM.…”

“…In 2 patients (P5, P6) with severe congenital pancytopenia, we detected the mutation c.2248C.T (p.Arg750Trp) previously reported for 3 other patients with RUSAT2. 6,7,9 Both were platelet and erythrocyte transfusion dependent from birth and experienced severe recurrent bacterial and fungal infections. Radiographs for upper extremities revealed no anomalies; RUS could be excluded in P5 ( Figure 2C).…”

“…Major phenotypic differences existed within families (eg, P1 and P2), and in 2 of our patients without RUS, we found a MECOM mutation identical to that previously described for 3 patients with RUSAT2. 6,7,9 Other genetic or epigenetic factors presumably influence the phenotypic characteristics.…”

“…Recently, 2 other patients with RUSAT2 were described, 7,8 and Bluteau et al 9 identified 6 patients with MECOM mutations in a large cohort of patients with IBMFSs (supplemental Table 1). …”