PRENATAL-DIAGNOSIS OF UNIPARENTAL DISOMY-15 FOLLOWING TRISOMY-15 MOSAICISM

Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent of Prader-Willi syndrome cases, is usually caused by mater nal meiosis I non-disjunction associated with advanced maternal age. T hese cases may initially be detected as mosaic trisomy 15 during routi ne prenatal,diagnostic studies. In such cases, PCR (polymerase chain r eaction) microsatellite analysis of uncultured cells makes prospective prenatal diagnosis for UPD15 possible with results available in 2-4 d ays. We have performed molecular analyses on a series of seven cases o f mosaic trisomy 15 identified in amniotic fluid (AF, n=3) or chorioni c villus samples (CVS, n=4) from patients initially referred for advan ced maternal age or abnormal triple screen. In all cases, the maternal ages were greater than or equal to 35 years and maternal meiosis I no n-disjunction was documented as the cause of the trisomy in all inform ative cases (n=5). Of the three cases with mosaic trisomy 15 at amnioc entesis, two showed the presence of the trisomy in the fetus. Molecula r analysis showed one case with maternal UPD15 in the euploid cell, li ne and one case with biparental inheritance. Both of these families el ected to terminate the pregnancies based on the presence of true fetal mosaicism. In the third case, low-level trisomy 15 mosaicism in the a mniotic fluid was not confirmed in a follow-up amniotic fluid sample a nd molecular analysis indicated biparental inheritance in the fetus. F or the four trisomy 15 mosaics detected at CVS, molecular analysis was performed on direct amniotic fluid cell lysates for prospective diagn osis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic analysis of the amniotic fluid in all four cases was normal, indicating confirm ed placental mosaicism. Molecular analysis showed one of these four ca ses to have maternal heterodisomy 15. Based on the likelihood of Prade r-Willi syndrome due to maternal UPD15, the couple chose to terminate the pregnancy. The total of two of seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the theoretical expectation of one-third and indicates a high risk of UPD in such pregnancies. Theref ore, UPD testing should be offered in all cases of mosaic trisomy 15 e ncountered in CVS dr amniocentesis.