Objective To analyse the results of the first 2 years of a QF-PCR stand-alone testing strategy for the prenatal diagnosis of aneuploidy in the London region and to determine the advantages and disadvantages of this policy.Methods A review of the results of 9737 prenatal samples received for exclusion of chromosome abnormalities. All samples were subjected to QF-PCR testing for common aneuploidies but only samples fulfilling specific criteria subsequently had a full karyotype analysis. ResultsOf the 9737 samples received, 10.3% had a chromosome abnormality detected by QF-PCR testing. Of the 7284 samples received with no indication for karyotype analysis, 25 (0.3%) received a normal QF-PCR result but subsequently had an abnormal karyotype detected either prenatally as a privately funded test or postnatally. Of these samples, without subsequent abnormal ultrasound findings, five had a chromosome abnormality associated with a poor prognosis, representing 0.069% of samples referred for Down syndrome testing.Conclusion While back-up karyotyping is required for some samples, using QF-PCR as a stand-alone prenatal test for pregnancies without ultrasound abnormalities reduces costs, provides rapid delivery of results, and avoids ambiguous and uncertain karyotype results, reducing parental anxiety.

Delineating the genetic causes of developmental disorders is an area of active investigation. Mosaic structural abnormalities, defined as copy number or loss of heterozygosity events that are large and present in only a subset of cells, have been detected in 0.2–1.0% of children ascertained for clinical genetic testing. However, the frequency among healthy children in the community is not well characterized, which, if known, could inform better interpretation of the pathogenic burden of this mutational category in children with developmental disorders. In a case–control analysis, we compared the rate of large-scale mosaicism between 1303 children with developmental disorders and 5094 children lacking developmental disorders, using an analytical pipeline we developed, and identified a substantial enrichment in cases (odds ratio = 39.4, P-value 1.073e − 6). A meta-analysis that included frequency estimates among an additional 7000 children with congenital diseases yielded an even stronger statistical enrichment (P-value 1.784e − 11). In addition, to maximize the detection of low-clonality events in probands, we applied a trio-based mosaic detection algorithm, which detected two additional events in probands, including an individual with genome-wide suspected chimerism. In total, we detected 12 structural mosaic abnormalities among 1303 children (0.9%). Given the burden of mosaicism detected in cases, we suspected that many of the events detected in probands were pathogenic. Scrutiny of the genotypic–phenotypic relationship of each detected variant assessed that the majority of events are very likely pathogenic. This work quantifies the burden of structural mosaicism as a cause of developmental disorders.

Background and study aims Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP) (EDGE) is a novel technique for managing pancreaticobiliary diseases in patients with a history of Roux-en-Y Gastric Bypass (RYGB). It has shown to have high technical success rates and fewer adverse events as compared to laparoscopic-assisted ERCP (LA-ERCP). We compared the technical success and clinical outcomes of EDGE vs. LA-ERCP vs. E-ERCP. Patients and methods A retrospective chart review was performed for 56 patients, of whom 18 underwent LA-ERCP, 12 underwent E-ERCP, and 26 had EDGE, and a comparison of technical success and complication rates was done. Results Baseline demographic characteristics of patients undergoing these procedures, including age and gender, were comparable. The technical success rate for patients in the EDGE group were 100 % (n = 26), compared with 94 % (n = 17) and 75 % (n = 9) in the LA-ERCP and E-ERCP groups (P = 0.02). In the EDGE group, 8 % of patients (n = 2) had bleeding, and 4 % of patients (n = 1) had lumen-apposing metal stent migration occur during the procedure. In the LA-ERCP group 6 % (n = 1) of patient had bleeding, 6 % (n = 1) post-ERCP pancreatitis and 6 % (n = 1) were diagnosed with an intra-abdominal infection post-procedure. Time to complete the EDGE procedure was significantly shorter at 79 ± 31 mins, compared with 158 ± 50 mins for LA-ERCP and 102 ± 43 mins for E-ERCP (P < 0.001). Conclusion EDGE is a novel procedure with short procedure times and an effective alternative to LA-ERCP and E-ERCP in management of pancreaticobiliary diseases in patients with a history of RYGB.