There are no mutations in DS-epi1 associated with human diseases. However, mutations in D4ST1, which functionally collaborates with DS-epi1 to make IdoA blocks (Fig. 3), result in adducted thumb-clubfoot syndrome 32. Mutations of D4ST1 result in reduced amount of IdoA in CS/DS 25, also resulting in a defect in collagen fibril maturation and reduced collagen strength 28. This autosomal recessive syndrome 33 is characterized by facial changes, contractures of thumbs and fingers, joint instability, skin hyperextensibility, and heart and kidney defects. Additionally, myopathy has been described in these patients 34.
