A bilaterally blind woman, with a three generation family history of autosomal dominant congenital cataracts, variably associated with iris colobomata and microcornea, sought preconception genetic consultation. Whole-exome sequencing was performed in three affected family members, one unaffected first degree relative, and one spouse. The sequence variant c.168C>G; p.(Tyr56∗) in CRYGD, previously reported as pathogenic, and a novel mutation c.809C>A; p.(Ser270Tyr) in MAF, were identified in two affected family members; the grandmother, and half-brother of the proband. The proband inherited only the MAF mutation, whereas her clinically unaffected sister had the CRYGD change. In silico analysis supported a pathogenic role of p.(Ser270Tyr) in MAF, which was absent from publicly available whole-exome datasets, and 1161 Czech individuals. The frequency of CRYGD p.(Tyr56∗) in the ExAC dataset was higher than the estimated incidence of congenital cataract in the general population. Our study highlights that patients with genetically heterogeneous conditions may exhibit rare variants in more than one disease-associated gene, warranting caution with data interpretation, and supporting parallel screening of all genes known to harbour pathogenic mutations for a given phenotype. The pathogenicity of sequence variants previously reported as cataract-causing may require re-assessment in light of recently released datasets of human genomic variation.

Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia.

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Poster abstracts different occasions (intraobserver variability) or between different examiners (interobserver variability) was calculated by using intraclass correlation coefficient (ICC) and Bland-Altman graphs. Results: It was observed high intra-and interobserver agreement with ICC > 0.90 for all 3D power Doppler indices in the ACA territory. Intraobserver reliability: VI [ICC = 0.984 (CI 95% 0.959-0.994)], FI [ICC = 0.985 (CI 95% 0.962-0.994)], VFI [ICC = 0.986 (CI 95% 0.964-0.994)]. Interobserver reliability: VI [ICC = 0.960 (CI 95% 0.899-0.984)], FI [ICC = 0.983 (CI 95% 0.958-0.993)], VFI [ICC = 0.916 (CI 95% 0.910-0.926)]. Conclusions: This method to study ACA territory proved to be practical, easy and with high intra-and interobserver reproducibility. P25.10 Use of three-dimensional (3D) sonography to assess the true midsagittal plane of fetal spine

Oral communication abstractsdiameter in the three vessels and trachea view. This ratio was measured in a cross sectional study on 302 normal healthy fetuses between 15 and 39 weeks gestation and related to gestational age for reference ranges. The study group consisted of 90 fetuses with different CHD and a normal karyotype and of 20 fetuses with CHD and a proven del.22q11. Results: The TT-Ratio of normal fetuses did not show any statistically significant change during gestation with a mean value of 0.44. Values of 90 fetuses with CHD and no del.22q11 were within the normal range. However 19/20 (95%) fetuses with a proven del.22q11 had a significantly smaller TT-Ratio (P < 0.001) with a mean of 0.25. Conclusions:The study shows that the TT-Ratio can be easily achieved during fetal echocardiography. In normal fetuses it is constant throughout gestation with no need to compare to reference ranges. Fetuses with a low TT-Ratio are at high risk to be associated with del.22q11 and targeted FISH analysis is then recommended. OC28.02BACs on beads: a clue to ultrasound findings

There was a spacing error in the initial online publication, and there were errors in the Acknowledgments section. The original article has been updated.The online version of the original article can be found under

Objectives: To evaluate the prenatal sonographic and postnatal findings associated with absent ductus venosus and porto-systemic shunts. Methods: A retrospective search was conducted on databases and clinical records of patients attended in our Fetal Medicine Unit between years 2005-2013. Associated anomalies and obstetric and perinatal outcomes were recorded. Results: Seven cases of absent ductus venosus and porto-systemic shunts were identified over a 37,035 fetuses scanned. The diagnosis was made in seven cases at first trimester scan, in two at 20 weeks scan and in five in later scans. The umbilical vein was connected to the intrahepatic abdominal part of the inferior vena cava in four cases (4/7, 57.1%), in one case (1/7, 14.3%) the connection was totally extrahepatic, directly into the right atrium and in the remaining two cases (2/7, 28.3%) a mixed pattern, with a normal umbilical vein connection to the portal sinus and an aberrant extrahepatic channel into infrahepatic inferior vena cava and right iliac vein, was respectively seen. Hydropic changes, including an isolated polyhydramnios, was seen in three cases (3/7, 42.9%) and cardiomegaly in two cases (2/7, 28.6%). Hydropic changes or cardiomegaly were present in all three cases of extrahepatic shunt. Major anomalies were detected in two fetuses (2/7, 28.6%) and anomalous karyotype (Down's syndrome) in one (1/7, 14.3%). No miscarriages or postnatal deaths were detected. All but one shunts spontaneously closed in the first months after birth, and one spontaneously closed prenatally. Conclusions: Absent ductus venosus and porto-systemic shunts frequently occur in association with major fetal anomalies or chromosomal defects, so careful search for associated anomalies and fetal karyotyping should be considered. Cardiac overload and hydropic changes are also frequent. Prognosis is mainly determined by the severity of associated anomalies.

Purpose To identify the molecular genetic cause in a three generation family with the occurrence of congenital cataracts, variably associated with iris colobomata and microcornea. Methods Whole‐exome sequencing was performed in three affected family members, one unaffected first degree relative, and one spouse. Sequence variants previously reported as disease‐causing, and novel sequence variants within genes listed in CatMap (http://cat-map.wustl.edu/) were given a priority for further evaluation. Verification of possibly pathogenic sequence variants was performed by conventional Sanger sequencing. Results Sequence variant c.168C>G; p.(Tyr56*) in CRYGD, previously reported as pathogenic, and a novel mutation c.809C>A; p.(Ser270Tyr) in MAF, were identified in two affected family members; the grandmother, and half‐brother of the proband. The proband inherited only the MAF mutation, whereas her clinically unaffected sister had the CRYGD change. In silico analysis supported a pathogenic role of p.(Ser270Tyr) in MAF, which was absent from publicly available whole‐exome datasets, and 1,161 Czech individuals. The frequency of CRYGD p.(Tyr56*) in the ExAC dataset was higher than the estimated incidence of congenital cataract in the general population. Conclusions Our study highlights that patients with genetically heterogeneous conditions may exhibit rare variants in more than one disease‐associated gene, warranting caution with data interpretation, and supporting parallel screening of all genes known to harbour pathogenic mutations for a given phenotype. The pathogenicity of sequence variants previously reported as cataract‐causing may require re‐assessment in light of recently released datasets of human genomic variation. Supported by AZV 17‐30500A.