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.
Original language | English (US) |
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Pages (from-to) | 1826-1835 |
Number of pages | 10 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 191 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2023 |
Keywords
- MECOM
- aplastic anemia
- bone marrow failure
- inherited bone marrow failure syndrome
- radioulnar synostosis
- thrombocytopenia
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)