Expanding the phenotypic and genetic spectrum of radioulnar synostosis associated hematological disease

MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants

“…In humans, disruption of MECOM can cause (or is associated with) diseases. Typically, MECOM germline variants can cause RUSAT and/or bone marrow failure 4,5,9,10 ; its inversion or translocation causes acute myeloid leukemia, 21 and its overexpression is related to a poor outcome in patients with acute myeloid leukemia. 22 So far, the correlation between MECOM and human diseases was mainly investigated by focusing on the phenotypes of hematopoiesis.…”

“…Among them, MECOM was of high priority because mutant MECOM has been previously reported in patients with RUSAT 4 and in several patients with RUS originating from families with hematopoietic disease. 5,9,10 Sanger sequencing confirmed that the MECOM variant (c.2341C>T:p.R781C) cosegregated with disease in the family (Figure 1B).…”

“…7 Interestingly, there have been several members of the RUSAT families (or the families with hematopoietic disorders) with HOXA11 or MECOM variants who have only exhibited RUS only. 5,6,9,10 Recently, we have identified that 44 of 436 patients with sporadic RUS were affected by sex chromosome aneuploidy, 16 of 39 (41%) RUS pedigrees and 61 of 436 (14%) patients with sporadic RUS harbored SMAD6 variants, and 1 of 39 (3%) RUS pedigrees and 2 of 436 (0.5%) patients with sporadic RUS harbored NOG variants (unpublished data). 7,11 Nevertheless, a considerable number of patients with RUS have unknown genetic causes.…”

A Novel MECOM Variant Associated with Congenital Amegakaryocytic Thrombocytopenia and Radioulnar Synostosis

“…To the Editor Congenital radioulnar synostosis (RUS) is a rare developmental anomaly of proximal fusion of the radius and ulna, resulting in limited pronation and supination of the forearm. It may accompany other abnormalities in the skeleton, kidney, heart and aneuploidy syndromes 1,2 . A subset of patients with RUS present with bone marrow failure (BMF) syndromes, characterized by amegakaryocytic thrombocytopenia (RUSAT), progressing to myelodysplasia and pancytopenia 2,3 .…”

“…Heterozygous germline variants in the homeobox A11 (HOXA11) gene were the first to be associated with RUS and designated RUSAT1 4 , but lately, several families have been described with variants in the MDS1 and EVI1 complex (MECOM) locus, and referred to as RUSAT2 2,5,6 . Many of these variants appear de novo , while others follow an autosomal dominant inheritance.…”