title: Prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta associated with unaffected parents and paternal gonadal mosaicism.
abstract: OBJECTIVE
  To present the prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta (OI) associated with unaffected parents and paternal gonadal mosaicism.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Cytogenetic 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.
  
  
  CONCLUSIONS
  Recurrent 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.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Su
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000649:Amniocentesis; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D009030:Mosaicism; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016216:Ultrasonography, Prenatal
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005819:Genetic Markers