Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the 
genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Recently, 
dysregulation of hydroxylation of a single proline residue at position 986 of 
both the triple-helical domains of type I collagen alpha1(I) and type II 
collagen alpha1(II) chains has been implicated in the pathogenesis of recessive 
forms of OI. Two proteins, cartilage-associated protein (CRTAP) and 
prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that 
performs the hydroxylation and brings the prolyl cis-trans isomerase 
cyclophilin-B (CYPB) to the unfolded collagen. In our screen of 78 subjects 
diagnosed with OI type II or III, we identified three probands with mutations in 
CRTAP and 16 with mutations in LEPRE1. The latter group includes a mutation in 
patients from the Irish Traveller population, a genetically isolated community 
with increased incidence of OI. The clinical features resulting from CRTAP or 
LEPRE1 loss of function mutations were difficult to distinguish at birth. 
Infants in both groups had multiple fractures, decreased bone modeling 
(affecting especially the femurs), and extremely low bone mineral density. 
Interestingly, "popcorn" epiphyses may reflect underlying cartilaginous and bone 
dysplasia in this form of OI. These results expand the range of CRTAP/LEPRE1 
mutations that result in recessive OI and emphasize the importance of 
distinguishing recurrence of severe OI of recessive inheritance from those that 
result from parental germline mosaicism for COL1A1 or COL1A2 mutations.