Trace gas measurements in coastal Hong Kong during the PEM‐West B

Author name used in this publication: T. WangAuthor name used in this publication: K. S. LamVersion of RecordPublishe

MSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population

Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452-1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 1.5%) of 138 consecutive patients with early-onset CRC (93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide.published_or_final_versio

Array CGH testing in prenatal diagnosis: a promising new service with improved diagnostic yield and shortened reporting time

Eletronic Presentation: abstract no. 904Conference Theme: Enhancing Health - 協作同心‧醫澤社群INTRODUCTION: Array Comparative Genomic Hybridization (aCGH) with genome-wide coverage has proved to be valuable for postnatal and prenatal studies. Traditionally, prenatal diagnosis of chromosomal abnormalities has relied on conventional cytogenetics which required cell culture and chromosome analysis under micro…postprin

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for COVID-19 vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine Adverse Event Response and Evaluation Programme. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analysed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. 29 (87.88%) were males and 4 (12.12%) were females, with a median age of 15.25 years. 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management.The overall incidence of acute myocarditis/pericarditis was 18.52 (95% Confidence Interval [CI], 11.67-29.01) per 100,000 persons vaccinated. The incidence after the first and second doses were 3.37 (95%CI 1.12-9.51) and 21.22 (95%CI 13.78-32.28 per 100,000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI 2.38-12.53) and 37.32 (95% CI 26.98-51.25) per 100,000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose

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

Identification of a Key Amino Acid of LuxS Involved in AI-2 Production in Campylobacter jejuni

Autoinducer-2 (AI-2) mediated quorum sensing has been associated with the expression of virulence factors in a number of pathogenic organisms and has been demonstrated to play a role in motility and cytolethal distending toxin (cdt) production in Campylobacter jejuni. We have initiated the work to determine the molecular basis of AI-2 synthesis and the biological functions of quorum sensing in C. jejuni. In this work, two naturally occurring variants of C. jejuni 81116 were identified, one producing high-levels of AI-2 while the other is defective in AI-2 synthesis. Sequence analysis revealed a G92D mutation in the luxS gene of the defective variant. Complementation of the AI-2− variant with a plasmid encoded copy of the wild-type luxS gene or reversion of the G92D mutation by site-directed mutagenesis fully restored AI-2 production by the variant. These results indicate that the G92D mutation alone is responsible for the loss of AI-2 activity in C. jejuni. Kinetic analyses showed that the G92D LuxS has a ∼100-fold reduced catalytic activity relative to the wild-type enzyme. Findings from this study identify a previously undescribed amino acid that is essential for AI-2 production by LuxS and provide a unique isogenic pair of naturally occurring variants for us to dissect the functions of AI-2 mediated quorum sensing in Campylobacter

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Nuclear cataract is the most common type of age-related cataract and a leading cause ofblindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little isknown about specific genetic factors underlying this condition. Here we report findingsfrom the largest to date multi-ethnic meta-analysis of genome-wide association studies(discovery cohort N = 14,151 and replication N = 5299) of the International CataractGenetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468,P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10),LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1(rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of commongenetic variants in maintaining crystalline lens integrity in the aging eye

Avian influenza virus signaling: Implications for the disease severity of H5N1 infection

The global outbreak of avian influenza virus infections in poultry and wild birds as well as the high mortality rate in patients infected with the viruses pose a worldwide alert to the risk of an emerging epidemic. Scientific data to date showed some strains of avian influenza viruses including H5N1 are capable of going through mutations to develop into a novel, pandemic strain of influenza virus. Recent research has advanced our knowledge of the biological behavior of the virus, its interactions with mammalian cells, downstream signal transduction pathways, and the antiviral immune responses. A better understanding of the virus-activated signaling pathways will provide new clues to delineate the mechanisms underlying the pathogenesis of avian influenza virus infection. Here, we reviewed the contributions of human and avian influenza virus virulence factors including hemagglutinin HA, RNA polymerase, and nonstructural protein NS1. We next discussed the interaction of the viruses with cellular factors including Toll-like receptor TLR, RIG-I/MDA5, signaling kinases including PKR, MAPK and PI3K, and transcription factors NF-κB and IRF. Finally, we commented on the role of apoptosis and caspase activation as important host defense mechanisms. Taken together, virus replication and its activated inflammation contribute to the severity of avian influenza infections. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.link_to_subscribed_fulltex