Statistical approach to prenatal zygosity assessment following a decade of molecular aneuploidy screening.

In twin pregnancy studies, molecular genetic techniques have rarely been used to determine zygosity, despite their known precision and accuracy. The present work aimed to assess the power of discrimination in zygosity assessment, using a set of microsatellite markers that were routinely used for aneuploidy screening by multiplex-PCR in a prenatal context. Rapid aneuploidy screening using a group of 20 microsatellite markers (STRs) located on chromosomes 13, 18, 21 and X has been performed in our lab for over 10 years, with a total of approximately 1,500 samples studied to date. A retrospective analysis of the 257 prenatal samples from multiple pregnancies was carried out. A subset of 14 cases presenting theoretical monozygosity were re-evaluated by the use of biostatistics tools accessed via the ZygProb website. Further monozygosity determination relative to dizygosity was calculated, given an estimated overall error value of 0.093%. The results show that monozygosity had been correctly determined in all our previously studied twins. This work demonstrates that accurate zygosity assessment can be achieved with the same STRs applied in aneuploidy screening with a high power of discrimination and a matching probability of over 99.999999%.

A nonsense porcn mutation in severe focal dermal hypoplasia with natal teeth.

Focal dermal hypoplasia (FDH, Goltz syndrome), is an X-linked dominant mesoectodermal developmental disorder, involving skin, skeleton, eyes, teeth, and other organs. Mutations in PORCN, which stimulates the secretion of wingless family signal proteins, are found in FDH patients. A female fetus presented at 34 weeks gestation with interuterine growth restriction (IUGR), asymmetry, limb anomalies, microphthalmia, and lung anomaly. Focal dermal hypoplasia was confirmed at birth, with hypoplastic areas of skin, malformation of the limbs, diaphragmatic hernia, and ocular anomalies. Mutation analysis of PORCN revealed a nonsense mutation-Y359X. She presented natal teeth, an unexpected feature considering the role of the Wnt pathway in tooth development.