MOSAICISM FOR TRISOMY-12 - 4 CASES WITH VARYING OUTCOMES

Trisomy 12 observed in chorionic villus sampling (CVS) may reflect gen eralized mosaicism or indicate mosaicism confined to only the placenta . In this report, four cases of trisomy 12 observed in CVS or cultured placental biopsies with varying outcomes are presented. Seven dinucle otide repeat polymorphisms for chromosome 12 were used to determine th e chromosome 12 origins in the fetus or child and to delineate the mec hanism(s) that gave rise to the trisomy. In two cases (cases A and C), the mosaicism was confined to the placenta, resulting in normal liveb orns. Although, in one case, the molecular results suggested an appare nt duplication of one paternal chromosome 12 in the placenta, normal b iparental inheritance was found in the diploid fetal cell line in both cases. In two other cases (cases B and D), trisomy 12 was observed in both extraembryonic and fetal tissues. In one of these pregnancies, a child was born by Caesarean section at 37 weeks because of intrauteri ne growth retardation and oligohydramnios, and resulted in neonatal de ath. Molecular markers and fluorescence in situ hybridization (FISH) r evealed low-level trisomy 12 mosaicism in the spleen. In the fourth ca se, fetal abnormalities were detected on ultrasound and low-level tris omy 12 mosaicism was observed in amniotic fluid cells using convention al cytogenetics and FISH; Molecular markers revealed a maternal meiosi s I non-disjunction of chromosome 12 in DNA from a cultured placental biopsy. Although predicting the outcomes of pregnancies involving conf ined placental mosaicism remains difficult, molecular techniques are v aluable tools for distinguishing uniparental from biparental disomy an d mechanisms of mosaicism.