A novel mutation leading to elongation of the deduced α1(X) chain results in Metaphyseal Chondrodysplasia type Schmid

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1

“…In a murine model of SMCD, nonsense mutations lead to mRNA nonsense-mediated decay and haploinsufficiency. In SMCD, expressed mutant α1(X) chains are unable to trimerize to form a stable collagen and accumulate intracellularly leading to endoplasmic reticulum stress in hypertrophic chondrocytes [Zhu et al, 2011].…”

“…Radiographic findings include metaphyseal abnormalities, widening and irregularity of the growth plates, scoliosis [Park et al, 2015], shortening of tubular bones, coxa vara, and genu varum [Woelfle et al, 2011;Zhu et al, 2011;Wang et al, 2017]. The distal femoral and proximal tibial metaphyses are the most severely affected sites [Park et al, 2015], and the lumbar spine, anterior ribcage, forearms, and hands can also be affected [Woelfle et al, 2011].…”

“…Schmid-type metaphyseal chondrodysplasia (SMCD; MIM 156500) is an uncommon autosomal dominant skeletal dysplasia, characterized clinically by mild to moderate disproportionate short stature, short legs, bowing of the long bones, and a waddling gait [Woelfle et al, 2011;Zhu et al, 2011;Park et al, 2015;Higuchi et al, 2016;Wang et al, 2017]. Radiographic findings include metaphyseal abnormalities, widening and irregularity of the growth plates, scoliosis [Park et al, 2015], shortening of tubular bones, coxa vara, and genu varum [Woelfle et al, 2011;Zhu et al, 2011;Wang et al, 2017].…”

“…Type X collagen is a short chain, non-fibrillar collagen [Park et al, 2015] which is a homotrimeric molecule consisting of 3 identical α1(X) chains [Park et al, 2015;Higuchi et al, 2016]. Each α1(X) chain contains a core triplehelical domain, composed of uninterrupted repeats of the Gly-Xaa-Yaa tripeptide, flanked by 2 globular domains (noncollagenous domains [NC1] and [NC2]) at both the amino and carboxyl-terminal ends [Zhu et al, 2011;Higuchi et al, 2016]. Type X collagen is an extracellular matrix protein which is normally expressed in the hypertrophic zone of the growth plate adjacent to the calcifying cartilage [Mäkitie et al, 2005;Zhu et al, 2011].…”

“…Each α1(X) chain contains a core triplehelical domain, composed of uninterrupted repeats of the Gly-Xaa-Yaa tripeptide, flanked by 2 globular domains (noncollagenous domains [NC1] and [NC2]) at both the amino and carboxyl-terminal ends [Zhu et al, 2011;Higuchi et al, 2016]. Type X collagen is an extracellular matrix protein which is normally expressed in the hypertrophic zone of the growth plate adjacent to the calcifying cartilage [Mäkitie et al, 2005;Zhu et al, 2011]. Mutations in COL10A1 disrupt the growth plate function and endochondral ossification [Woelfle et al, 2011;Park et al, 2015;Wang et al, 2017].…”