%0 Journal Article
%T Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in MECOM-associated syndromes.
%A Lozano Chinga MM
%A Bertuch AA
%A Afify Z
%A Dollerschell K
%A Hsu JI
%A John TD
%A Rao ES
%A Rowe RG
%A Sankaran VG
%A Shimamura A
%A Williams DA
%A Nakano TA
%J Am J Med Genet A
%V 191
%N 7
%D 07 2023 17
%M 37067177
%F 2.578
%R 10.1002/ajmg.a.63208
%X The MECOM gene encodes multiple protein isoforms that are essential for hematopoietic stem cell self-renewal and maintenance. Germline MECOM variants have been associated with congenital thrombocytopenia, radioulnar synostosis and bone marrow failure; however, the phenotypic spectrum of MECOM-associated syndromes continues to expand and novel pathogenic variants continue to be identified. We describe eight unrelated patients who add to the previously known phenotypes and genetic defects of MECOM-associated syndromes. As each subject presented with unique MECOM variants, the series failed to demonstrate clear genotype-to-phenotype correlation but may suggest a role for additional modifiers that affect gene expression and subsequent phenotype. Recognition of the expanded hematologic and non-hematologic clinical features allows for rapid molecular diagnosis, early identification of life-threatening complications, and improved genetic counseling for families. A centralized international publicly accessible database to share annotated MECOM variants would advance their clinical interpretation and provide a foundation to perform functional MECOM studies.