COL1A1 and osteogenesis imperfecta: The mildest OI, type I, is often caused by heterozygous mutations in COL1A1, leading to nonsense mediated decay and haploinsufficiency.(6) Homozygous or compound heterozygous mutations causing complete lack of collagen I alpha 2 chain typically result in EDS with a defect in cardiac valve,(19, 20, 21) but in some cases they have been associated with moderate or severe OI.(22, 23, 24, 25) In addition, a mixed EDS/OI phenotype has been described.(26) There is no clear understanding of the mechanisms leading to differential outcomes of the lack of collagen I alpha2 chain.