Heterozygous variants in both MATN3 and COMP genes (pathological intracellular accumulation of defective proteins explain the dominant negative effect (50, 51) leading to a phenotype of multiple epiphyseal dysplasia (MED), a relatively heterogeneous condition characterized by short stature, delayed and irregular epiphyseal ossification and early onset osteoarthritis (52, 53). Here, MATN3 is linked to multiple epiphyseal dysplasia.