Genetic analysis, reproductive decision-making, and pregnancy outcomes in 51 Chinese osteogenesis imperfecta families

To elucidate the genetic etiology of osteogenesis imperfecta (OI) in affected families and to characterize reproductive decision-making, reproductive interventions, and pregnancy outcomes of these families.

Fifty-one families with clinically suspected OI underwent variant analysis by Sanger sequencing or next-generation sequencing (NGS) and clinical follow-up of reproductive options and pregnancy outcomes.

Of the 51 enrolled families, 37 probands had mild phenotypes and 14 presented with severe phenotypes. Genetic analysis revealed that 46 probands (90.2%) carried heterozygous variants in COL1A1 or COL1A2, and five (9.8%) harbored biallelic variants in WNT1, CRTAP, P3H1, and SERPINF1. Of the identified variants, 14 were novel. Among the 45 families with follow-up data, the proportion of couples who discontinued reproductive attempts was higher in the OI-women group than in the OI-men and normal-parent groups (35.3% vs. 5.9% and 18.2%, respectively), though the differences were not statistically significant. Both women with severe OI (n = 2) discontinued reproductive attempts, compared with 26.7% of women with mild OI. Thirty families underwent preimplantation genetic testing (PGT), which yielded 22 healthy live births. Among the remaining families, six (seven pregnancies) opted for spontaneous conception or conventional IVF with prenatal diagnosis, resulting in two terminations of affected fetuses and five healthy live births. The cesarean section rate in the OI-women group was significantly higher than that in the OI-men group (81.8% vs. 27.3%, P = 0.030), whereas the difference from the normal-parent group was not statistically significant (81.8% vs. 60.0%, P = 0.547). One woman with OI experienced reduced bone mineral density during pregnancy.

Our findings expand the OI mutational spectrum and suggest that reproductive decision-making may vary according to the sex of the affected parent, inheritance patterns, and phenotypic severity. A high cesarean section rate and skeletal complications were observed among women with OI during pregnancy, indicating that maternal and obstetric outcomes warrant careful attention in this population. Moreover, PGT was associated with healthy live births in this cohort and may reduce the likelihood of affected pregnancies in selected families.