{Reference Type}: Journal Article
{Title}: Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in MECOM-associated syndromes.
{Author}: Lozano Chinga MM;Bertuch AA;Afify Z;Dollerschell K;Hsu JI;John TD;Rao ES;Rowe RG;Sankaran VG;Shimamura A;Williams DA;Nakano TA;
{Journal}: Am J Med Genet A
{Volume}: 191
{Issue}: 7
{Year}: 07 2023 17
{Factor}: 2.578
{DOI}: 10.1002/ajmg.a.63208
{Abstract}: 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.