The Novel Association of a Single Nucleotide Variant in the COL3A1 Gene with Diffuse Coronary Aneurysms

Norgan Radler, Charlene; Ku, Kevin; Hodge, Alison; Wang, Tianci; Moore, Peyton; Sathyamoorthy, Mohanakrishnan

Item

The Novel Association of a Single Nucleotide Variant in the COL3A1 Gene with Diffuse Coronary Aneurysms

Norgan Radler, Charlene; Ku, Kevin; Hodge, Alison; Wang, Tianci; Moore, Peyton; Sathyamoorthy, Mohanakrishnan

Publisher

MDPI

Date

2025-01-27

Abstract

The COL3A1 gene, encoding the pro-alpha chain of type III collagen, has been implicated in a range of collagen-mediated diseases such as Ehlers–Danlos syndrome and aortic aneurysms. In this report, we present evidence for the first time associating a single nucleotide variant p.P517R in exon 22 of COL3A1 with the development of diffuse coronary aneurysms in a human subject without prior atherosclerotic cardiovascular disease, connective tissue disorder, or phenotypic characteristics diagnostic for vascular Ehlers–Danlos syndrome. Computational modeling of this specific variant in AlphaFold and in silico analyses predict deleterious alterations in the structure and function of the COL3A1 gene product, alpha 1 chain of type III collagen. This novel phenotype-to-genotype correlation should prompt further investigation into the mechanistic basis of this association.