Molecular characteristics

Molecular characteristics

MEOX1 (Mesenchyme Homeobox 1) gene is located at 17q21.31 and encodes a homeodomain-containing protein Meox1, which localizes to many mesodermal structures and appears to have a non-redundant role in the development of the sclerotome.  Although the mechanism by which Meox1 controls normal somite development is still incompletely understood, one proposed mechanism is that Meox1 maintains appropriate expression of Bapx1, Tbx18, and Uncx, which are genes known to regulate somite development. Knockout mouse models show segmentation defects in the cervical spine but normal muscle development, which is similar to the phenotype observed in individuals with MEOX1 mutations.

Mutations and pathophysiology

Mohamed et al. (2013) reported homozygosity for a nonsense mutation (c.664C>T), that created a premature stop codon (p.Arg222*) in one consanguineous family and a frameshift mutation, c.94delG [p.Ala32Profs*165] in another consanguineous family.

Bayrakli et al. (2013) reported homozygosity for c.670G>A [p.Gln84Ter] mutation in MEOX1.

As mentioned above, the proposed pathophysiological mechanism is that Meox1 physically binds the promoter of the Bapx1, Tbx18, and Uncx genes, which are associated with regulating somite development, and that its deficiency perturbs their expression domain. Meox1 deficiency is also associated with the diminution of the normal caudal/rostral polarity of the somites at the early stages of development.