Background: Non-invasive prenatal testing (NIPT) has been widely adopted for the detection of fetal aneuploidies and microdeletion syndromes, nevertheless, limited clinical utilization has been reported for the non-invasive prenatal screening of monogenic diseases. In this study, we present the development and validation of a single comprehensive NIPT for prenatal screening of chromosomal aneuploidies, microdeletions and 50 autosomal recessive disorders associated with severe or moderate clinical phenotype. Results: We employed a targeted capture enrichment technology powered by custom TArget Capture Sequences (TACS) and multi-engine bioinformatics analysis pipeline to develop and validate a novel NIPT test. This test was validated using 2033 cell-fee DNA (cfDNA) samples from maternal plasma of pregnant women referred for NIPT and paternal genomic DNA. Additionally, 200 amniotic fluid and CVS samples were used for validation purposes. All NIPT samples were correctly classified exhibiting 100% sensitivity (CI 89.7-100%) and 100% specificity (CI 99.8-100%) for chromosomal aneuploidies and microdeletions. Furthermore, 613 targeted causative mutations, of which 87 were unique, corresponding to 21 monogenic diseases, were identified. For the validation of the assay for prenatal diagnosis purposes, all aneuploidies, microdeletions and point mutations were correctly detected in all 200 amniotic fluid and CVS samples. Conclusions: We present a NIPT for aneuploidies, microdeletions, and monogenic disorders. To our knowledge this is the first time that such a comprehensive NIPT is available for clinical implementation.

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

The contribution of genetic variants to prostate cancer risk has been documented. Mutations in ACE (angiotensin I-converting enzyme) gene are found to be related with prostate cancer. The purpose of the present study was to characterize ACE genotypes in prostate cancer cases and to investigate any association between I/D polymorphisms of ACE gene and clinical characteristics in a group of Romanian patients. A total of 46 healthy men and 46 male patients diagnosed with prostate cancer were included in the study. ACE I/D polymorphisms were determined by polymerase chain reaction methodology. The highest genotype frequencies found within the prostate cancer group were detected for DD genotype (55.6%) with a significant difference in the allele frequencies (p = 0.006), compared to the control group, where no significant differences were observed (p > 0.05). The DD genotype was statistically significant associated with the advanced tumor stage and Gleason score higher than 8. Our data suggest that the ACE gene polymorphism can be associated with the evolution of prostate cancer disease, more precisely that DD genotype represented a risk factor for prostate cancer.

Objectives: to investigate the relationships between immune system and endothelial dysfunction in IUGR mother-child couple. Methods: 170 pregnant patients were included in the study . Adiponectin, leptin, tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and C reactive protein (CRP) in IUGR, small for gestational age (SGA) and appropriate for gestational age (AGA) mother-child couple at delivery were assessed. Fetal aorta intima media thickness (aIMT) was evaluated in the same fetal groups. IUGR fetuses were defined as fetuses whose estimated fetal weight (EFW) was below 10th percentile for gestational age with umbilical artery (UA) Doppler abnormalities. SGA fetuses were defined as fetuses whose EFW was below 10th percentile for gestational age with normal fetal velocimetry. Results: There were 37 IUGR mother-child couple, 33 SGA and 70 AGA ones. Maternal adiponectin concentration presented the same distribution among the three groups (p 0.137), while leptin, TNFα, IL-6 and CRP serum levels were higher in IUGR mothers than SGA and AGA pregnant patients (p 0.04, p 0.008, p 0.06 and p 0.04, respectively). If adiponectin levels were significantly reduced in IUGR fetuses than SGA and AGA ones, leptin (p < 0.05), TNFα (p 0.05) and IL-6 (p 0.05) levels conversely were higher in the former group, such as aIMT (<0.05). Moreover, fetal aIMT was significantly greater in IUGR group than SGA (p 0.0003) and AGA ones (p 0.0002), and SGA fetuses had a higher aIMT than AGA group (p 0.05). Finally, in IUGR fetuses there were a negative correlation between aIMT and adiponectin/leptin ratio (A/L ratio) (p < 0.05) and between adiponectin and IL-6 levels than SGA and AGA group (p < 0.05). Conclusions: In IUGR fetuses a higher fetal aIMT associated with decreased blood adiponectin levels and increased adipocytokines concentrations might relate to a greater risk of endothelial damage and insulin resistance. P13.22Intrauterine growth restriction, cerebellar hematoma and PMD C. Martínez-Payo, R. Alvarez Bernabéu, I. Salas Villar, E. Iglesias Obstetricia y Ginecologia, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, SpainPlacental mesenchymal dysplasia (PMD) is a rare vascular disease associated with intrauterine growth restriction, fetal demise as well as with Beckwick-Wiedemann syndrome. Some neonates present hematologic abnormalities possibly related to consumptive coagulopathy and hemolytic anemia in the placental circulation.A 31 year old pregnant woman on 21st week of pregnancy, the scan showed a fetus smaller than the gestational age, placentomegaly with hypoechoic areas, severe oligoamnios, a hyperechogenic intestine and hemorrhagic damage in the left hemisphere of the cerebellum.The middle cerebral artery speed was higher than average 1.5 MoM for the gestational age. The Karyotype was 46 XX. aCGH analysis revealed no genomic imbalance in the amniocytes. Higher than average concentrations of alfaprotein levels were foun in the amniotic fluid. The TORCH study revealed no abnormalities. Threee weeks later, the...

The aim of this study is to compare indications and approval rates of requests for late termination of pregnancy (LTOP) before and after the policy change in late 2007. Methods: A retrospective study of requests for LTOP and board decisions between 2002-2012 in three university affiliated medical centers. Patients were categorized as group 1 (requests between 2002-2007, before the policy change) and group 2 (2008-2012, after the policy change). Data regarding demographics, reason for application, approval or rejection, and actual termination of pregnancy were extracted. Comparisons between groups were performed by Student's T-test or ANOVA for ordinal data and Chi-Square for categorical data. Results: The database included 565 patients' applications for LTOP. The data of the groups including reasons for LTOP requests and rejections are presented in Table 1. The overall approval rate for LTOP, and the specific approval rate per medical indication were not significantly different between the groups. The rejection rate due to intrauterine infection increased in group 2 (9.1% vs. 26.3%, p = 0.09) but decreased due to pregnancy complications from 62.5% to 25.9% p = 0.06. The main anomalies for which LTOP request due to structural anomaly was denied because they were considered mild included cardiac, renal, cerebral and skeletal anomalies. Conclusions: The 2007 new rigid criteria for approval of request for LTOP made no difference in rejection rate of requests due to structural anomalies between the 2 periods. In the later period rejection rates due to intrauterine infection increased and due to pregnancy complications decreased but did not reach statistical significance.