Molecular Basis of Pathogenic Variants in the Fibrillar Collagens

Abstract

The fibrillar collagen family is comprised of the quantitatively major types I, II and III collagens and the quantitatively minor types V and XI. These form heterotypic collagen fibrils (composed of more than a single collagen type) where the minor collagens have a regulatory role in controlling fibril formation and diameter. The structural pre-requisites for normal collagen biosynthesis and fibrillogenesis result in many places where this process can be disrupted, and consequently a wide variety of phenotypes result when pathogenic changes occur in these fibrillar collagen genes. Another contributing factor is alternative splicing, both naturally occurring and as the result of pathogenic DNA alterations. This article will discuss how these factors should be taken into account when assessing DNA sequencing results from a patient.

Molecular analysis of the extracellular microenvironment: from form to function

“…The way that fibers assemble within the extracellular microenvironment have been known for decades to alter in disease status [38,39]. Alterations in extracellular assembly are driven by mutations, propeptide splice variants, changes in ECM composition or post-translational modifications, differential crosslinking and MMP activity [30,[40][41][42][43]. Subsequently, fiber measurements have been used to predict disease progression and outcome [39,44,45].…”