A simple and effective approach for detecting maternal cell contamination in molecular prenatal diagnosis

The presence of maternal cells in fetal samples constitutes a serious potential source for prenatal misdiagnosis. Here we present our approach for detecting maternal cell contamination (MCC) at prenatal diagnosis for eight monogenic disorders (autosomal recessive: β-thalassaemia, sickle-cell anaemia, cystic fibrosis, prelingual deafness; autosomal dominant: achondroplasia, Huntington disease, myotonic dystrophy, neurofibromatosis type I; X-linked: spinobulbar muscular atrophy). Our aim was to apply a simple and low-cost approach, which would easily and accurately provide information on the fetal tissue MCC status. MCC testing was applied to cases of recessive inheritance where the primary mutation screening of the fetus revealed the presence of the maternal mutation, to cases concerning dominant inheritance and to cases of multiple gestation. The potential presence of maternal cells was determined by the amplification of the 3′-HVR/APO B, D1S80, THO1 and VNTRI of vWf polymorphic loci, which have previously demonstrated high heterozygosity in Caucasians. Among 135 prenatal diagnoses, 44 finally needed to be tested for MCC (32.6%). MCC was detected in four cases, where DNA was isolated directly from chorionic villi samples (CVS), and in one case with DNA isolated directly from amniotic fluid (AF). In almost 90% of cases a simple test of one polymorphic locus provided sufficient information about MCC. The choice of the appropriate locus is therefore essential, while the simultaneous screening of both parents provides the means for distinguishing non-informative sites about MCC. Copyright © 2002 John Wiley & Sons, Ltd.     

Trisomy 12 mosaicism detected by mid–trimester amniocentesis

Trisomy 12 mosaicism was found in about 15 per cent of cultured amniocytes obtained from a 32-year-old white female at 17·6 weeks of gestation. Termination of pregnancy was elected and multiple tissues were obtained for chromosome analysis. Of 158 cells examined, only 1 cell in placenta was found with an extra number 12 chromosome. Pathological examination of the fetus did not reveal significant physical abnormalities. This report illustrates the difficulty of confirming trisomy 12 mosaicism which has been detected on prenatal diagnosis. The presence of trisomy 12 in one placental cell obtained from the curettage specimen suggests the possibility of confined placental mosaicism in this case.