title: A father of four consecutive trisomic pregnancies with elevated frequencies of associated aneuploid sperm.
abstract: A couple with normal somatic karyotypes had four consecutive trisomic pregnancies, each involving a different chromosome, of which two children were liveborn with confirmed paternal-origin trisomies. The apparently healthy father produced abnormally high frequencies of disomic sperm for each of the four chromosomes involved in the trisomic pregnancies (P< 0.003, by sperm fluorescence in situ hybridization (FISH)). His elevated sperm aneuploidies persisted over a 2-year period and affected all chromosomes evaluated, suggesting that he had a genome-wide defect in meiotic disjunction. He also had the highest frequencies of aneuploid sperm reported for any healthy man to date. His frequencies of aneuploid sperm were comparable to the peak frequencies of the transient responses reported in some cancer patients after receiving aneugenic chemotherapies. These findings indicate that apparently healthy men can produce abnormally high frequencies of sperm aneuploidies that suggest that this condition may contribute to recurrent trisomic pregnancies.
authors.affiliation: Biosciences Directorate, Lawrence Livermore National Laboratory (LLNL), Livermore, California, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Tomascik-Cheeseman
authors.forename: Xiu R
authors.initials: XR
authors.lastname: Lowe
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.forename: Sharon
authors.initials: S
authors.lastname: Kidd
authors.forename: Joginder
authors.initials: J
authors.lastname: Nath
authors.forename: Dan
authors.initials: D
authors.lastname: Moore
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
mesh_terms: D000328:Adult; D000782:Aneuploidy; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D014314:Trisomy