Rapid aneuploidy testing (knowing less) versus traditional karyotyping (knowing more) for advanced maternal age: What would be missed, who should decide?

Objectives The application of rapid aneuploidy testing as a stand-alone approach in prenatal diagnosis is much debated. The major criticism of this targeted approach is that it will not detect other chromosomal abnormalities that will be picked up by traditional karyotyping. This study aimed to study the nature of such chromosomal abnormalities and whether parents would choose to terminate affected pregnancies. Design Retrospective study on a cytogenetic database. Setting Eight public hospitals in Hong Kong. Participants The karyotype results of 19 517 amniotic fluid cultures performed for advanced maternal age (≥35 years) from 1997 to 2002 were classified according to whether they were detectable by rapid aneuploidy testing. The outcomes of pregnancies with abnormal karyotypes were reviewed from patient records. Results In all, 333 (1.7%) amniotic fluid cultures yielded abnormal karyotypes; 175 (52.6%) of these were detected by rapid aneuploidy testing, and included trisomy 21 (n=94, 28.2%), trisomy 18 or 13 (n=21, 6.3%), and sex chromosome abnormalities (n=60, 18.0%). The other 158 (47.4%) chromosomal abnormalities were not detectable by rapid aneuploidy testing, of which 63 (18.9%) were regarded to be of potential clinical significance and 95 (28.5%) of no clinical significance. Pregnancy outcomes in 327/333 (98.2%) of these patients were retrieved. In total, 143 (42.9%) of these pregnancies were terminated: 93/94 (98.9%) for trisomy 21, 20/21 (95.2%) for trisomy 18 or 13, 19/60 (31.7%) for sex chromosome abnormalities, and 11/63 (17.5%) for other chromosomal abnormalities with potential clinical significance. There were no terminations in the 95 pregnancies in which karyotyping results were regarded to be of no clinical significance. Conclusions 'Knowing less' by the rapid aneuploidy stand-alone testing could miss about half of all chromosomal abnormalities detectable by amniocentesis performed for advanced maternal age. Findings from two fifths of the latter were of potential clinical significance, and the parents chose to terminate one out of six of the corresponding pregnancies. If both techniques are available, parents could have enhanced autonomy to choose.published_or_final_versio

Effectiveness of a Technology-Based Injury Prevention Program for Enhancing Mothers’ Knowledge of Child Safety: Protocol for a Randomized Controlled Trial

Protocolpublished_or_final_versio

Diagnostic value of whole-exome sequencing in Chinese pediatric-onset neuromuscular patients

BACKGROUND: Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with a broad spectrum of overlapping the clinical presentations that makes diagnosis challenging. Notably, the recent introduction of whole-exome sequencing (WES) is introducing rapid changes on the genetic diagnosis of NMDs. We aimed to investigate the diagnostic value of WES for pediatric-onset NMDs. METHODS: We applied integrated diagnostic approach and performed WES in 50 Chinese subjects (30 males, 20 females) with undiagnosed pediatric-onset NMDs despite previous specific tests. The patients were categorized in four subgroups according to phenotyping and investigation findings. Variants on NMDs gene list and open exome analysis for those with initial negative findings were identified. RESULTS: WES identified causative variants in ACTA1 (n = 2), POMT1, COL6A1 (n = 2), MTMR2, LMNA, SELENON, DNM2, TGFB1, MPZ, IGHMBP2, and LAMA2 in 13 patients. Two subjects have variants of uncertain significance (VUSs) in TTN and SCN11A, unlikely to be pathogenic due to incompatible phenotypes. The mean interval time from symptom onset to genetic diagnosis was 10.4 years (range from 1 month to 33 years). The overall diagnostic yield of WES in our cohort was 26%. Open exome analysis was necessary to identify the pathogenic variant in TGFB1 that caused skeletal dysplasia with neuromuscular presentation. CONCLUSION: Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

published_or_final_versio

Copy number variation in Hong Kong patients with autism spectrum disorder

Oral Free Paper Session: Oral Presentation 6 [best oral presentation]BACKGROUND AND AIMS: When offering chromosomal microarray for patients with autism spectrum disorder (ASD), as according to international standards, copy number variations of uncertain significance (CNV VUS) are frequently identified, which leads to challenges in genetic counselling. We aim to study the CNV findings in children with ASD in Hong Kong, and to gather information for reclassification of recurrent CNV VUS. METHODS: ASD patients from the Department of Paediatrics and Adolescent Medicine QMH/HKU were recruited if their Array Comparative Genomic Hybridization (aCGH) were done anytime from January 2011 to August 2014 in Prenatal Diagnostic Laboratory, Tsan Yuk Hospital. Diagnosis of ASD was made by developmental paediatricians and clinical psychologists using the criteria from Diagnostic and Statistical Manual of Mental Disorders, Fourth or Fifth Edition. NimbleGen CGX-135k oligonucleotide array and Agilent CGX 60k oligonucleotide array were used. Information was summarised from the literature and existing databases to re-classify CNV VUS occurring in our ASD cohort. RESULTS: Among 288 patients with ASD in our cohort, we identified 5 patients with pathogenic CNV (1.74%) and 5 patients with likely pathogenic CNV (1.74%). Among all the CNV VUS, one variant overlapping DPP10 (hg[19] chr2:116,534,689-116,672,358) was recurrently found in Chinese individuals. The frequency of this variant in our ASD cohort was 0.35% (1 in 288), and 0.96% (9 in 935) in our controls. (P=0.467, two-tailed Fisher’s exact test). Similar CNVs were suggested to be ASD-related in previous studies recruiting mainly Caucasians. However, there were Chinese individuals with typical development possessing similar CNVs identified in independent sources (9 from our internal database, 1 from Singapore Genome Variation Project, 24 from The Singapore Prospective Study Program). CONCLUSIONS: Our study explored the CNV findings in Hong Kong paediatric ASD patients. The CNV overlapping DPP10 may be a Chinese-related copy-number variation in Hong Kong Chinese, and we reclassified it to be likely benign in our locality. Our result emphasized the need to account for ethnicity to give the most precise interpretation of aCGH data.published_or_final_versio

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Wind Shear Forecasting by Chaotic Oscillatory-based Neural Networks (CONN) with Lee Oscillator (Retrograde Signalling) Model

Version of RecordPublishe

Histological findings in a case of alobar holoprosencephaly diagnosed at 10 weeks of pregnancy

A case of alobar holoprosencephaly diagnosed at 10 + 3 weeks' gestation by transabdominal and transvaginal ultrasound examination followed by histological confirmation is presented. The diagnosis was based on two sonographic criteria: intracranial finding of a single ventricle with a mantle and no visible midline structures but fusion of the thalami and corpus striatum, and facial abnormalities, including hypotelorism and proboscis. The fetal karyotype was triploidy. The ultrasound findings were confirmed by pathological examination. The histological findings of proboscis, single lens and single ventricle with neural tissue remnants are presented.link_to_subscribed_fulltex

Functional categorization of carbapenemase-mediated resistance by a combined genotyping and two-tiered Modified Hodge Test approach

2014-2015 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe