Molecular Basis of Pathogenic Variants in the Fibrillar Collagens

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.

Automated summary

The fibrillar collagen family consists of major types I, II, III collagens and minor types V, XI. These collagens form heterotypic collagen fibrils that are regulated by the minor collagens, controlling their formation and size. Disruptions in the collagen biosynthesis process and alternative splicing can lead to various phenotypes. This article discusses the importance of considering these factors when analyzing DNA sequencing results from patients.