Parental origin of the extra chromosome in prenatally diagnosed fetal trisomy 21

Trisomy 21 (Down syndrome) is one of the most common chromosomal abnormalit ies. Of cases of free trisomy 21 causing Down syndrome, about 95% result fr om nondisjunction during meiosis, and about 5% are due to mitotic errors in somatic cells. Previous studies using DNA polymorphisms of chromosome 21 s howed that paternal origin of trisomy 21 occurred in only 6.7% of cases. Ho wever, these studies were conducted in liveborn trisomy 21-affected infants , and the possible impact of fetal death was not taken into account. Using nine distinct DNA polymorphisms, we tested 110 families with a prenatally d iagnosed trisomy 21 fetus. Of the 102 informative cases, parental origin wa s maternal in 91 cases (89.2%) and paternal in 11 (10.8%). This percentage differs significantly from the 7.0% observed in previous studies (P<0.001). In order to test the influence of genomic parental imprinting, we determin ed the origin of the extra chromosome 21 in relation to different factors: advanced maternal age, maternal serum human chorionic gonadotropin (hormone of placental origin), severity of the disease, gestational age at diagnosi s and fetal gender. We found that the increased frequency of paternal origi n of nondisjunction in trisomy 21-affected fetuses cannot obviously be expl ained by Factors leading to selective loss of paternal origin fetuses.