Prenatal Diagnosis of Osteogenesis Imperfecta: Review of 183 Diagnostic Studies From 1985 to 1998.

Melanie Pepin and Peter H. Byers.
University of Washington, Seattle.

Between 1985 and 1998 we studied 183 pregnancies at risk for osteogenesis imperfecta (OI). Studies in 154 pregnancies were completed by analysis of collagen synthesized by cells cultured from chorionic villus biopsies. In the remaining 29 we searched for known mutations (N=20) in COL1A1 or COL1A2 or used polymorphic restriction sites in the COL1A1 gene (N=9) to determine if the fetus had inherited the previously identified mutant allele. Samples were submitted for prenatal testing in 77 pregnancies at risk for OI type II, 56 for OI type III, 27 for OI type IV, and 23 for OI type I. There were 2 classes of samples, that in which unaffected parents had had one (115) or more (13) affected children, and that in which one parent was affected (55). There were 4 recurrences in 115 pregnancies to unaffected parents with on eprevious affected, and 2 recurrences in nine pregnancies (22%) of unaffected couples had had two previous affected pregnancies with OI type II.

There were 55 pregnancies in which one parent had osteogenesis imperfecta. In these instances, there were 27 affected pregnancies (51%). Pregnancies at risk for OI type I could not be ascertained reliably by biochemical studies of cultured CVS cells but were identified by either direct analysis of the causative mutation or by the use of linked markers in the family.

Of the 154 biochemical studies completed there were no false positive results and a single false negative result that was probably a result of contamination of chorionic villi with maternal cells. In the 20 molecular genetic studies accuracy of test results was 100%. Linkage studies looking at polymorphic markers in COL1A1 were 100% accurate when informative. Diagnostic results were available within 20-30 days of biopsy by biochemical studies and by 10-14 days by molecular studies.

Reference: Proceedings of the 7th International Conference on Osteogenesis Imperfecta. Montreal, Canada, 1999.