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Objective: The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics., Methods: We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing., Results: High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion., Conclusion: High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance., (© 2014 John Wiley & Sons, Ltd.)

Objective: It is generally believed that monochorionic-diamniotic twin pregnancies result from one fertilized oocyte with both siblings having the same genotype and phenotype. In rare instances, due to somatic mutations or chromosome aberrations, the karyotypes and phenotypes of the two twins can differ., Method: We report cytogenetic, molecular genetic and clinical examinations in monochorionic-diamniotic twins discordant in gender., Results: The monochorionic-diamniotic status of the twins was diagnosed by ultrasound and histologic examination of the placenta. Prenatal chromosome examination performed on amniocytes revealed a normal female karyotype in one and a 46,XX(26)/46,XY(3) karyotype in the other twin. Molecular examinations confirmed monozygosity despite discordant sex. Based on the cytogenetic and molecular results of lymphocytes and placental cells, the only explanation for gender discordance was that the conceptus originally had a 47,XXY chromosome complement., Conclusion: A 47,XXY zygote appears to have undergone a twinning process. A postzygotic loss of the X chromosome in some cells and the Y chromosome in other cells, either before or after twinning, resulted in 46,XX/46,XY mosaicism in both monozygotic (MZ) twins. The sex discordance of the MZ twins can be explained by different proportions of the 46,XX and 46,XY cell lines in the gonads and other tissues., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Objective: To investigate the origin and mechanisms of formation of isochromosomes 13q and 21q in instances where prenatal chromosome examination revealed a normal karyotype while postnatal chromosome examination from blood showed translocation trisomy 13 and 21., Methods: G and/or Q-banded chromosome examinations from CVS cultures and lymphocyte chromosome examinations from two newborns. Microsatellite marker analysis of DNA from the probands and their parents. Prenatal ultrasonic examinations of the fetuses and postnatal clinical examinations of the probands., Results: Short and long-term CVS examinations from two fetuses revealed normal karyotypes. Lymphocyte karyotypes of the newborns showed the karyotype 46,XY,i(21)(q10) in the first case and 46,XY,i(13)(q10) in the second. The isochromosomes 21q and 13q were shown, by microsatellite marker analysis of the patients and their parents, to be of maternal and paternal origin, respectively., Conclusion: Postzygotic isochromosome formation is one of the possible mechanisms that may lead to false-negative results of chorionic villus chromosome examinations, even if both short-term and long-term cultures are performed and give normal results., (2006 John Wiley & Sons, Ltd.)

Prenatal ultrasound identified Dandy-Walker malformation (DWM) in ten singleton pregnancies with concurrent central nervous system (CNS) anomalies and extra-CNS anomalies in eight cases. DWM was confirmed by postnatal magnetic resonance imaging (MRI) or pathological examination in nine cases. Karyotypes were normal in the seven infants tested. Postnatal neurological and developmental testing in the five survivors showed a spectrum of clinical outcome from minor defects to severe handicap. Postnatal investigation also disclosed additional CNS and extra-CNS findings not detected on ultrasound, as did autopsy in the other five infants. However, ultrasound diagnosis of DWM is accurate and is an indication for exhaustive screening for concurrent anomalies both within and outside the CNS and in chromosome structure and number, as the prognosis is heavily dependent on associated malformations and karyotype., (Copyright 2000 John Wiley & Sons, Ltd.)