Several mutations in the COL1A2 gene are responsible for the ‘Arthrochalasia Type’ of Ehlers-Danlos Syndrome (EDS). These mutations, which affect one copy of the COL1A2 gene in each cell, delete a segment of the pro-α2 (I) chain that attaches one collagen molecule to another. The absence of this important segment prevents the normal assembly of type I collagen fibrils and alters the cross-linking between collagen molecules. These changes mainly affect tissues that are rich in type I collagen, such as the skin, bones, and tendons.
Rarely, mutations in both copies of the COL1A2 gene in each cell have been reported in people with the characteristic features of Ehlers-Danlos syndrome. These mutations prevent cells from producing any normal pro-α2 (I) chains. As a result, type I collagen fibrils in the skin and other tissues cannot be assembled correctly. The presence of abnormal collagen is associated with a variety of signs and symptoms, including loose joints, cardiac problems and other complications associated with Ehlers-Danlos syndrome.