Prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta associated with unaffected parents and paternal gonadal mosaicism

ObjectiveTo present the prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta (OI) associated with unaffected parents and paternal gonadal mosaicism.Materials and MethodsA 37-year-old woman was referred for genetic counseling at 18 weeks of gestation because of advanced maternal age and a family history of OI. The woman had a daughter who was affected with OI type III and carried an insertion frameshift mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. The woman and her husband were non-consanguineous and healthy. Amniocentesis was performed at 18 weeks of gestation.ResultsCytogenetic analysis revealed a karyotype of 46,XX. Molecular analysis of the amniocytes revealed a recurrent mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. Mutational analysis of the family revealed no mutation of the COL1A1 gene in the parental bloods. However, mosaicism for the COL1A1 mutation was found in the paternal sperms. Level II ultrasound examination showed a curved right tibia, a narrow chest with irregular ribs and mild frontal bossing in the fetus. The parents decided to terminate the pregnancy, and a female fetus was delivered at 23 weeks of gestation with curved long bones.ConclusionRecurrent autosomal dominant OI may occur in the offspring of unaffected parents with parental gonadal mosaicism. Genetic counseling of recurrent autosomal dominant OI should include a thorough mutational analysis of the family members, and mutational analysis of the sperm may detect paternal gonadal mosaicism for the mutation.