Using knockdown in cell culture and gene ablation in mice we have directly compared the roles of ATF6α & β in responding to the increased ER stress induced by mutant forms of type X collagen that cause the ER stress-associated metaphyseal chondrodysplasia type Schmid (MCDS).
We did not, however, detect mutations in the coding and non-coding regions of COL10A1 in one subject with MCDS, the subject with atypical MCDS, and in the nine subjects with other forms of metaphyseal chondrodysplasia.
The cloning of bovine and then human collagen type X genes facilitated studies in relevant human diseases and contributed to the discovery of mutations in the COL10A1 gene in families with metaphyseal chondrodysplasia type Schmid.
Carbamazepine reduces disease severity in a mouse model of metaphyseal chondrodysplasia type Schmid caused by a premature stop codon (Y632X) in the Col10a1 gene.
Cartilage-hair hypoplasia diagnosis should be considered in patients with metaphyseal chondrodysplasia even in the absence of any extra-skeletal manifestations if no mutation in COL10A1 can be found and the family history is compatible with autosomal recessive inheritance.
COL10A1 nonsense and frame-shift mutations have a gain-of-function effect on the growth plate in human and mouse metaphyseal chondrodysplasia type Schmid.
Early-onset metaphyseal chondrodysplasia type Schmid associated with a COL10A1 frame-shift mutation and impaired trimerization of wild-type α1(X) protein chains.
Metaphyseal chondrodysplasia type Schmid (MCDS) is caused by mutations in COL10A1 that are clustered in the carboxyl-terminal non-collagenous (NC1) encoding domain.
Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia.