WES is a promising method for the identification of genetic variants that cause structural abnormalities in fetuses with normal results on karyotyping and CMA. This enhanced diagnostic yield has the potential to improve the clinical management of pregnancies and to inform better the reproductive decisions of affected families. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267-Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P 5 5.7 3 10 223 , odds ratio 5 0.36) irrespective of hepatitis B virus surface antibody status (P 5 6.2 3 10 221 and 1.5 3 10 210 , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P 5 0.007). The estimated heritability explained by this single variation was 3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion: The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (HEPATOLOGY 2015;61:1251-1260 C hronic hepatitis B (CHB) affects approximately 240 million people worldwide and is responsible for about 780,000 deaths annually (http://www.who.int/mediacentre/factsheets/fs204/en/).Clinically, CHB holds the most significant medical consequences among hepatitis B virus (HBV)-infected individuals. Acute-on-chronic liver failure (ACLF) is the most urgent and lethal condition related to CHB.Abbreviations: ACLF, acute-on-chronic liver failure; AIM, ancestry-informative marker; ASBT, apical sodium-dependent bile acid transporter; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBsAb, hepatitis B virus surface antibody; HBsAg, hepatitis B virus surface antigen; HDV, hepatitis D virus; NTCP, sodiumtaurocholate cotransporting polypeptide..From the

Objective To evaluate the clinical performance of non-invasive prenatal testing (NIPT) in detecting fetal copy number variants (CNVs). Methods

Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.