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Background: Antley-Bixler syndrome (ABS) is an exceptionally rare craniosynostosis syndrome that can be accompanied by disordered steroidogenesis, and is mainly caused by mutations in the POR gene, inherited in an autosomal recessive manner. Here we report the prenatal and postmortem findings of three sibling fetuses with ABS as a result of compound heterozygosity of a paternal submicroscopic deletion and a maternal missense mutation in the POR gene., Methods: Prenatal ultrasound and postmortem examination were performed in three sibling fetuses with termination of pregnancy at 22, 23, and 17 weeks of gestation, respectively. Molecular analysis of fetus 2 and 3 included (a) bidirectional sequencing of exon 8 of the POR gene after amplification of the specific locus by polymerase chain reaction, to detect single nucleotide variants (SNVs) and (b) high resolution comparative genomic hybridization (CGH) positive single nucleotide polymorphism array CGH (aCGH) analysis to detect copy number variants (CNVs), copy neutral areas of loss of heterozygosity and uniparental disomy., Results: The diagnosis of ABS was suggested by the postmortem examination findings. The combination of the POR gene molecular analysis and aCGH revealed a compound heterozygous genotype of a maternal SNV (p.A287P) and a paternal CNV (NC_000007.13:g.(?_75608488)_(75615534_?)del)., Conclusion: To the best of our knowledge, these sibling fetuses add to the few reported cases of ABS, caused by a combination of a SNV and a CNV in the POR gene. The detailed description of the pathologic and radiographic findings of second trimester fetuses affected with ABS adds novel knowledge concerning the early ABS phenotype, in lack of previous relevant reports. Birth Defects Research (Part A) 106:536-541, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

BACKGROUND Cat-Eye syndrome (CES) with teratoma has not been previously reported. We present the clinical and molecular findings of a 9-month-old girl with features of CES and also a palpable midline neck mass proved to be an extragonadal mature teratoma, additionally characterized by array comparative genomic hybridization (aCGH). RESULTS High resolution oligonucleotide-based aCGH confirmed that the supernumerary marker chromosome (SMC) derived from chromosome 22, as was indicated by molecular cytogenetic analysis with fluorescence in situ hybridization (FISH). Additionally, aCGH clarified the size, breakpoints, and gene content of the duplication (dup 22q11.1q11.21; size:1.6 Mb; breakpoints: 15,438,946-17,041,773; hg18). The teratoma tissue was also tested with aCGH, in which the CES duplication was not found, but the analysis revealed three aberrations: del Xp22.3 (108,864-2788,689; 2.7 Mb hg18), dup Yp11.2 (6688,491-7340,982; 0.65 Mb, hg18), and dup Yq11.2q11.23 (12,570,853-27,177,133; 14.61 Mb, hg18). These results indicated 46 XY (male) karyotype of the teratoma tissue, making this the second report of mature extragonadal teratoma in a female neonate, probably deriving from an included dizygotic twin of opposite sex (fetus in fetu). CONCLUSIONS Our findings extend the phenotypic spectrum of CES syndrome, a disorder with clinical variability, pointing out specific dosage-sensitive genes that might contribute to specific phenotypic features., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Pelizaeus-Merzbacher disease (PMD) is a recessive, X-linked leukoencephalopathy attributed to impaired myelination during central nervous system development, caused by defects in the proteolipid protein 1 (PLP1) gene. PMD presents clinical variability, ranging from the severe connatal form to the classic form., Cases: We report the clinical and molecular findings of two affected males, three carrier females, and an aborted male fetus with familial PMD. The two male probands presented with severe PMD phenotype and intellectual disability. High-resolution oligonucleotide-based array comparative genomic hybridization (aCGH) identified an Xq22.2 duplication of 320.6 kb (102641391-102961998, hg18), including the PLP1 gene and surrounding chromosomal region. Postmortem examination of the aborted fetus at 25 weeks' gestation showed focal subcortical white matter degeneration, focal gliosis, and cerebellar atrophy., Conclusions: Genotype-phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the PLP1 gene has a more complex role in human brain development, exceeding its structural function in myelin formation., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Identification of fetal nucleated red blood cells (NRBCs) in maternal circulation can facilitate non-invasive prenatal diagnosis, but technical difficulties still exist. An increase in the number of circulating NRBCs, however, could indicate fetal aneuploidies or pregnancy complications., Materials and Methods: The number of NRBCs was determined from 20 mL peripheral blood in 351 women in the second trimester of pregnancy after isolation by magnetic cell sorting (MACS) with anti-CD71 antibody and identification with May-Grunwald/Giemsa staining., Results: An average of eight NRBCs (range 1-12) were identified among 282 women with chromosomally normal fetuses. In cases known to carry aneuploid fetuses the mean number was 35 (range 7-113), but when the fetus had trisomy 21 (n = 17) an average of 71 NRBCs were identified. Among 26 carriers of beta-thalassemia, 42 NRBCs (range 22-158) were isolated. In pregnancies with abnormal Doppler findings in both uterine arteries (n = 20), 15 NRBCs (range 2-75) were isolated., Conclusion: Determining the number of NRBCs in maternal circulation could represent an additional screening step for fetal aneuploidies, as long as the anemic status of the mother is taken into consideration. However, more cases with abnormal Doppler results must be investigated before this test is used for in the prediction of pregnancy complications., ((c) 2006 John Wiley & Sons, Ltd.)