MEIOTIC ORIGIN OF TRISOMY IN CONFINED PLACENTAL MOSAICISM IS CORRELATED WITH PRESENCE OF FETAL UNIPARENTAL DISOMY, HIGH-LEVELS OF TRISOMY IN TROPHOBLAST, AND INCREASED RISK OF FETAL INTRAUTERINE GROWTH RESTRICTION

Molecular studies were performed on 101 cases of confined placental mo saicism (CPM) involving autosomal trisomy. The origin of the trisomic cell line was determined in 54 cases (from 51 pregnancies), 47 of whic h were also analyzed for the presence of uniparental disomy (UPD) in t he disomic cell line. An additional 47 cases were analyzed for parenta l origin in the disomic cell line only. A somatic (postmeiotic) origin of the trisomy was observed in 22 cases and included the majority of cases with CPM for trisomy 2, 7, 8, 10, and 12. Most cases of CPM invo lving trisomy 9, 16, and 22 were determined to be meiotic. Fetal mater nal UPD was found in 17 of 94 informative CPM cases, involving trisomy 2 (1 case), 7 (1 case), 16 (13 cases), and 22 (2 cases). The placenta l trisomy was of meiotic origin in all 17 cases associated with fetal UPD (P = .00005). A meiotic origin also correlated with the levels of trisomy in cultured chorionic villi samples (CVS) (P = .0002) and trop hoblast (P = .00005). Abnormal pregnancy outcome (usually IUGR) correl ated with meiotic origin (P = .0003), the presence of fetal UPD (P = 4 x 10(-7)), and the level of trisomy in trophoblast (P = 3 x 10(-7)) b ut not with the level of trisomy in CVS or term chorion. The good fit of somatic errors with the expected results could have been observed o nly if few true meiotic errors were misclassified by these methods as a somatic error. These data indicate that molecular determination of o rigin is a useful predictor of pregnancy outcome, whereas the level of trisomy observed in cultured CVS is not. In addition, UPD for some ch romosomes may affect prenatal, but not postnatal, development, possibl y indicating that imprinting effects for these chromosomes are confine d to placental tissues.