The presence of chromosomally abnormal cells in a single culture of amniocytes with only normal cells in all other cultures is consdiered to represent pseudomosaicism since the fetus is usually found to have a normal karyotype. We have recently shown that advanced maternal age is associated with maternal uniparental disomy (UPD) of chromosome 15 in Praeder-Willi syndrome (PWS) and proposed that UPD arises from a trisomy 15 zygote that subsequently loses the paternal chromosome. Based on our concern about the origin of UPD in PWS (and likewise, in Angelman syndrome; AS), we carried out cytogenetic and molecular studies on a prenatal case involving pseudomosaicism for Trisomy 15. We were able to distinguish between UPD and normal biparental inheritance, thus addressing the potential concern regarding the risk of a fetus with PWS or AS.

A 34 year-old G5 P2022 female and her husband were referred for consideration of amniocentesis. Following counseling, the couple elected to pursue maternal serum a-fetoprotein screening at 16 weeks gestation. A 0.66 adjusted MOM was obtained, which increased her age-related risk of carrying a child with Down syndrome from 1 in 417 to 1 in 290. The couple remained concerned about the pregnancy, and pursued amniocentesis at 17 weeks gestation. Chromosomal analysis of 2 coverslips revealed a normal female kareotype, 46,XX. Four flasks were subsequently harvested, of which 3 showed only normal cells (53 metaphase spreads analyzed). In the remaining flask, however, two of the twenty-five metaphases counted had a karyotype of 47, XX+15.

Parental blood samples were obtained at 19 weeks gestation for cytogenetic analysis. The chromosome 15 heteromorphisms were not distinctive enough to permit differentiation of the maternal and paternal chromosomes. Therefore, molecular studies were initiated at 20 weeks gestation. Four highly informative, polymorphic genetic loci were studied in order to distinguish between biparental and disomic inheritance. Both maternal and paternal alleles were inherited for 2 of these markers, D15S86 and c-fes; the remaining markers were uninformative. The family was notified of these results at approximately 23 weeks gestation.

Uniparental disomy is no longer a rare curiosity, having now been reported for at least 10 of the human chromosomes. Our case report illustrates the practical concern which arises when mosaicism is observed for a chromosome known or suspected to contain gene(s) whose expression is modified by genomic imprinting. Furthermore, this case raises both ethical and legal considerations once investigational studies begin to impact on the provision of prenatal care.

The full text of this article is available in PDF format from Springer Online, in "Journal of Genetic Counseling Archived Issues".