Which gene mutation is most commonly associated with Ehlers Danlos Syndrome Classic type?

The most commonly associated gene mutations with Ehlers-Danlos Syndrome (EDS) Classic type are in the COL5A1 and COL5A2 genes. EDS Classic type primarily affects the synthesis of type V collagen, which is crucial for the structural integrity of connective tissues. Type V collagen is a component of the extracellular matrix and plays a significant role in the regulation of collagen fibril organization.

Mutations in COL5A1 and COL5A2 lead to the characteristic features of Classic type EDS, including skin hyperextensibility, joint hypermobility, and a tendency to bruise easily. These gene mutations impair collagen structure and function, resulting in weakened connective tissues.

In comparison, mutations in COL1A1 and COL3A1 can cause other forms of EDS and connective tissue disorders, but they are not primarily responsible for EDS Classic type. Similarly, while ACTA2 mutations are associated with vascular-related disorders, they are not the primary contributors to the Classic type of EDS. Thus, the correct association with EDS Classic type lies with the mutations in COL5A1 and COL5A2 genes.