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