75 results on '"Brian Hon-Yin Chung"'
Search Results
2. P588: De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome characterized by hypotonia, epilepsy, and short stature
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Kevin Booth, Sharayu Jangam, Martin Man Chun Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Kerry White, Celanie Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy Tsang, Sally Lynch, Sureni Mullegama, Julia Baptista, Daniela Iancu, Shelag Joss, Christopher CY Mak, Anna Kwong, Hugo Bellen, Erin Conboy, Remo Sanges, Michael F. Wangler, Brian Hon-Yin Chung, and Francesco Vetrini
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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3. O17: GestaltMatcher supports classification of ultra-rare disorders and delineation of novel syndromes by facial phenotype descriptors
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Hannah Klinkhammer, Hellen Lesmann, Shahida Moosa, Alexander Hustinx, Behnam Javanmardi, Jing-Mei Li, Martin M.C. Chui, Christopher C.Y. Mak, Luisa Averdunk, Felix Distelmaier, Brian Hon-Yin Chung, Peter Krawitz, and Tzung-Chien Hsieh
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Genetics ,QH426-470 ,Medicine - Published
- 2023
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4. Functional Evaluation and Genetic Landscape of Children and Young Adults Referred for Assessment of Bronchiectasis
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Jeffrey Fong Ting Chau, Mianne Lee, Martin Man Chun Chui, Mullin Ho Chung Yu, Jasmine Lee Fong Fung, Christopher Chun Yu Mak, Christy Shuk-Kuen Chau, Ka Ka Siu, Jacqueline Hung, Kit San Yeung, Anna Ka Yee Kwong, Christopher O'Callaghan, Yu Lung Lau, Chun-Wai Davy Lee, Brian Hon-Yin Chung, and So-Lun Lee
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exome sequencing ,genome sequencing ,early-onset bronchiectasis ,transmission electron microscopy ,high-speed video microscopy ,primary ciliary dyskinesia ,Genetics ,QH426-470 - Abstract
Bronchiectasis is the abnormal dilation of the airway which may be caused by various etiologies in children. Beyond the more recognized cause of bacterial and viral infections and primary immunodeficiencies, other genetic conditions such as cystic fibrosis and primary ciliary dyskinesia (PCD) can also contribute to the disease. Currently, there is still debate on whether genome sequencing (GS) or exome sequencing reanalysis (rES) would be beneficial if the initial targeted testing results returned negative. This study aims to provide a back-to-back comparison between rES and GS to explore the best integrated approach for the functional and genetics evaluation for patients referred for assessment of bronchiectasis. In phase 1, an initial 60 patients were analyzed by exome sequencing (ES) with one additional individual recruited later as an affected sibling for ES. Functional evaluation of the nasal nitric oxide test, transmission electron microscopy, and high-speed video microscopy were also conducted when possible. In phase 2, GS was performed on 30 selected cases with trio samples available. To provide a back-to-back comparison, two teams of genome analysts were alternatively allocated to GS or rES and were blinded to each other’s analysis. The time for bioinformatics, analysis, and diagnostic utility was recorded for evaluation. ES revealed five positive diagnoses (5/60, 8.3%) in phase 1, and four additional diagnoses were made by rES and GS (4/30, 13%) during phase 2. Subsequently, one additional positive diagnosis was identified in a sibling by ES and an overall diagnostic yield of 10/61 (16.4%) was reached. Among those patients with a clinical suspicion of PCD (n = 31/61), the diagnostic yield was 26% (n = 8/31). While GS did not increase the diagnostic yield, we showed that a variant of uncertain significance could only be detected by GS due to improved coverage over ES and hence is a potential benefit for GS in the future. We show that genetic testing is an essential component for the diagnosis of early-onset bronchiectasis and is most effective when used in combination with functional tools such as TEM or HSVM. Our comparison of rES vs. GS suggests that rES and GS are comparable in clinical diagnosis.
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- 2022
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5. Exome sequencing in paediatric patients with movement disorders
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Anna Ka-Yee Kwong, Mandy Ho-Yin Tsang, Jasmine Lee-Fong Fung, Christopher Chun-Yu Mak, Kate Lok-San Chan, Richard J. T. Rodenburg, Monkol Lek, Shushu Huang, Sander Pajusalu, Man-Mut Yau, Cheung Tsoi, Sharon Fung, Kam-Tim Liu, Che-Kwan Ma, Sheila Wong, Eric Kin-Cheong Yau, Shuk-Mui Tai, Eva Lai-Wah Fung, Nick Shun-Ping Wu, Li-Yan Tsung, Jan Smeitink, Brian Hon-Yin Chung, and Cheuk-Wing Fung
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Movement disorders ,Whole exome sequencing ,Genetic diagnosis ,Treatment ,Medicine - Abstract
Abstract Background Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusions A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
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- 2021
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6. Invasive cerebral phaeohyphomycosis in a Chinese boy with CARD9 deficiency and showing unique radiological features, managed with surgical excision and antifungal treatment
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Sophie H.Y. Lai, Jaime S. Rosa Duque, Brian Hon-Yin Chung, Tom Wai-Hin Chung, Daniel Leung, Ronnie Siu-Lun Ho, Raymand Lee, Rosana W.S. Poon, Gilbert T. Chua, Kai-Ning Cheong, Martin Man Chun Chui, Mianne Lee, Sidney Tam, Andrew Ho Cheuk Him, King-Fai Cheng, Wilson Wai-Shing Ho, Kwok-Yung Yuen, Pamela Lee, and Yu-Lung Lau
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Cerebral Phaeohyphomycosis ,CARD9 deficiency ,Voriconazole therapeutic drug monitoring ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.
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- 2021
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7. Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss
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Sarah Wing-yiu Poon, Brian Hon-yin Chung, Anita Man-ching Tsang, and Grace Wing-kit Poon
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background. While the endocrine manifestations of pseudohypoparathyroidism are well known, less is known about the associated brain and spine abnormalities. These abnormalities may present with nonspecific symptoms in the paediatric population, and lack of awareness to these uncommon manifestations of the disease may result in a delay in necessary intervention. Case Presentation. We herein present a case of known pseudohypoparathyroidism type 1a who presented initially with minor head injury. She later developed progressive worsening headache, increased irritability, and vomiting. Repeated imaging showed hydrocephalus and Chiari malformation type 1 necessitating emergency craniectomy. Conclusion. Growth hormone deficiency, a common manifestation of pseudohypoparathyroidism type 1a, results in underdevelopment of the posterior cranial fossa and may account for the higher incidence of Chiari malformation in this group of patients. Other associated neurological features reported in pseudohypoparathyroidism type 1a include spinal stenosis, syringomyelia, and craniosynostosis. While less commonly seen, awareness to these associations is important in order to optimize the multidisciplinary care to this group of patients.
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- 2020
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8. Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism
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Kit San Yeung, Winnie Wan Yee Tso, Janice Jing Kun Ip, Christopher Chun Yu Mak, Gordon Ka Chun Leung, Mandy Ho Yin Tsang, Dingge Ying, Steven Lim Cho Pei, So Lun Lee, Wanling Yang, and Brian Hon-Yin Chung
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Somatic mosaicism ,Macrocephaly ,Megalencephaly ,Developmental delay ,Autism spectrum disorder ,PTEN ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Macrocephaly, which is defined as a head circumference greater than or equal to + 2 standard deviations, is a feature commonly observed in children with developmental delay and/or autism spectrum disorder. Although PTEN is a well-known gene identified in patients with this syndromic presentation, other genes in the PI3K-AKT-mTOR signalling pathway have also recently been suggested to have important roles. The aim of this study is to characterise the mutation spectrum of this group of patients. Methods We performed whole-exome sequencing of 21 patients with macrocephaly and developmental delay/autism spectrum disorder. Sources of genomic DNA included blood, buccal mucosa and saliva. Germline mutations were validated by Sanger sequencing, whereas somatic mutations were validated by droplet digital PCR. Results We identified ten pathogenic/likely pathogenic mutations in PTEN (n = 4), PIK3CA (n = 3), MTOR (n = 1) and PPP2R5D (n = 2) in ten patients. An additional PTEN mutation, which was classified as variant of unknown significance, was identified in a patient with a pathogenic PTEN mutation, making him harbour bi-allelic germline PTEN mutations. Two patients harboured somatic PIK3CA mutations, and the level of somatic mosaicism in blood DNA was low. Patients who tested positive for mutations in the PI3K-AKT-mTOR pathway had a lower developmental quotient than the rest of the cohort (DQ = 62.8 vs. 76.1, p = 0.021). Their dysmorphic features were non-specific, except for macrocephaly. Among the ten patients with identified mutations, brain magnetic resonance imaging was performed in nine, all of whom showed megalencephaly. Conclusion We identified mutations in the PI3K-AKT-mTOR signalling pathway in nearly half of our patients with macrocephaly and developmental delay/autism spectrum disorder. These patients have subtle dysmorphic features and mild developmental issues. Clinically, patients with germline mutations are difficult to distinguish from patients with somatic mutations, and therefore, sequencing of buccal or saliva DNA is important to identify somatic mosaicism. Given the high diagnostic yield and the management implications, we suggest implementing comprehensive genetic testing in the PI3K-AKT-mTOR pathway in the clinical evaluation of patients with macrocephaly and developmental delay and/or autism spectrum disorder.
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- 2017
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9. Genome-Wide DNA Methylation Analysis of Chinese Patients with Systemic Lupus Erythematosus Identified Hypomethylation in Genes Related to the Type I Interferon Pathway.
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Kit San Yeung, Brian Hon-Yin Chung, Sanaa Choufani, Mo Yin Mok, Wai Lap Wong, Christopher Chun Yu Mak, Wanling Yang, Pamela Pui Wah Lee, Wilfred Hing Sang Wong, Yi-An Chen, Daria Grafodatskaya, Raymond Woon Sing Wong, Chak Sing Lau, Daniel Tak Mao Chan, Rosanna Weksberg, and Yu-Lung Lau
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Medicine ,Science - Abstract
Epigenetic variants have been shown in recent studies to be important contributors to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report a 2-step study of discovery followed by replication to identify DNA methylation alterations associated with SLE in a Chinese population. Using a genome-wide DNA methylation microarray, the Illumina Infinium HumanMethylation450 BeadChip, we compared the methylation levels of CpG sites in DNA extracted from white blood cells from 12 female Chinese SLE patients and 10 healthy female controls.We identified 36 CpG sites with differential loss of DNA methylation and 8 CpG sites with differential gain of DNA methylation, representing 25 genes and 7 genes, respectively. Surprisingly, 42% of the hypomethylated CpG sites were located in CpG shores, which indicated the functional importance of the loss of DNA methylation. Microarray results were replicated in another cohort of 100 SLE patients and 100 healthy controls by performing bisulfite pyrosequencing of four hypomethylated genes, MX1, IFI44L, NLRC5 and PLSCR1. In addition, loss of DNA methylation in these genes was associated with an increase in mRNA expression. Gene ontology analysis revealed that the hypomethylated genes identified in the microarray study were overrepresented in the type I interferon pathway, which has long been implicated in the pathogenesis of SLE.Our epigenetic findings further support the importance of the type I interferon pathway in SLE pathogenesis. Moreover, we showed that the DNA methylation signatures of SLE can be defined in unfractionated white blood cells.
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- 2017
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10. Copy number variation and autism: New insights and clinical implications
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Brian Hon-Yin Chung, Victoria Qinchen Tao, and Winnie Wan-Yee Tso
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autism spectrum disorder ,chromosome microarray ,copy number variation ,genetic counseling ,genetic testing ,Medicine (General) ,R5-920 - Abstract
Genomic research can lead to discoveries of copy number variations (CNVs) which can be a susceptibility factor for autism spectrum disorder (ASD). The clinical translation is that this can improve the care of children with ASD. Chromosome microarray is now the first-tiered genetic investigation for ASD, with a detection rate exceeding conventional cytogenetics and any single gene testing. However, interpretation of the results is challenging and there is no consensus on “what” and “how much” to disclose. In this article, we will review how CNV studies have improved our understanding of ASD, the clinical applications, and related counseling issues. Future direction of autism genetic research is also discussed.
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- 2014
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11. Simpson-Golabi-Behmel syndrome type 1 with normal birth parameters.
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Brian Hon Yin Chung, Shu-ling Sophie Yeow, Joshua Chun Ki Chan, and Mianne Lee
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A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed a large-for-gestational-age foetus with a large abdominal circumference and liver, ventricular septal defect, right prominent renal pelvis and echogenic bowel. Antenatal genetic tests for overgrowth syndromes were negative. The mother had early onset pre-eclampsia. After birth, an overgrowth syndrome was still suspected despite the baby having normal birth parameters. Raw data of the trio whole exome sequencing from the amniocentesis sample were manually inspected. Hemizygous exon 7 deletion in the GPC3 gene was found, and a postnatal diagnosis of Simpson-Golabi-Behmel syndrome, a rare overgrowth syndrome, was made. This case report discusses the significance of antenatal findings, an atypical presentation of a rare syndrome and the obstacles of diagnostic genetic testing. [ABSTRACT FROM AUTHOR]
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- 2024
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12. NGS4THAL, a One-Stop Molecular Diagnosis and Carrier Screening Tool for Thalassemia and Other Hemoglobinopathies by Next-Generation Sequencing
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Yujie Cao, Shau-yin Ha, Chi-Chiu So, Ming-for Tony Tong, Clara Sze-man Tang, Huoru Zhang, Rui Liang, Jing Yang, Brian Hon-Yin Chung, Godfrey Chi-Fung Chan, Yu Lung Lau, Maria-Mercè Garcia-Barcelo, Edmond Shiu-Kwan Ma, Pranee Sucharitchan, Nattiya Hirankarn, and Wanling Yang
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Hemoglobinopathies ,Hemoglobins ,Mutation ,High-Throughput Nucleotide Sequencing ,Humans ,Thalassemia ,Molecular Medicine ,Pathology and Forensic Medicine - Abstract
Thalassemia is one of the most common genetic diseases and a major health threat worldwide. Accurate, efficient, and scalable analysis of next-generation sequencing (NGS) data is much needed for its molecular diagnosis and carrier screening. We developed NGS4THAL, a bioinformatics analysis pipeline analyzing NGS data to detect pathogenic variants for thalassemia and other hemoglobinopathies. NGS4THAL realigns ambiguously mapped NGS reads derived from the homologous Hb gene clusters for accurate detection of point mutations and small insertions/deletions. It uses a combination of complementary structural variant (SV) detection tools and an in-house database of control data containing specific SVs to achieve accurate detection of the complex SV types. Detected variants are matched with those in HbVar (A Database of Human Hemoglobin Variants and Thalassemia Mutations), allowing recognition of known pathogenic variants, including disease modifiers. Tested on simulation data, NGS4THAL achieved high sensitivity and specificity. For targeted NGS sequencing data from samples with laboratory-confirmed pathogenic Hb variants, it achieved 100% detection accuracy. Application of NGS4THAL on whole genome sequencing data from unrelated studies revealed thalassemia mutation carrier rates for Hong Kong Chinese and Northern Vietnamese that were consistent with previous reports. NGS4THAL is a highly accurate and efficient molecular diagnosis tool for thalassemia and other hemoglobinopathies based on tailored analysis of NGS data and may be scaled for population carrier screening.
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- 2022
13. Fibrodysplasia ossificans progressiva in Hong Kong—A case report series
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Joshua Chun Ki Chan, Evelyn Eugenie Kuong, Joyce Pui Kwan Chan, Ho Ming Luk, Jasmine Lee Fong Fung, Joanna Yuet-ling Tung, and Brian Hon Yin Chung
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Pediatrics, Perinatology and Child Health - Abstract
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare condition. The diagnosis could be challenging due to its rarity and non-specific presenting symptoms. However, early diagnosis and appropriate management help in preserving patients' function and quality of life. Herein, we report the diagnostic journeys and clinical courses of 8 patients with FOP in Hong Kong and illustrate the challenges involved.
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- 2023
14. Diazoxide-unresponsive Hyperinsulinemic Hypoglycaemia in a Preterm Infant with Heterozygous Insulin Receptor Gene Mutation
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Sarah Wing-yiu POON, Brian Hon-yin CHUNG, Mabel Siu-chun WONG, and Anita Man-ching TSAN
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Pediatrics, Perinatology and Child Health - Published
- 2023
15. The Effect of Communicating Genetic Risk of Type 2 Diabetes and Wearable Technologies On Wearable-Device-Measured Behavioral Outcomes in East Asians: Protocol of a Randomized Controlled Trial
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Youngwon Kim, Job Godino, Flora Lai Tung Cheung, Multhaup Michael, Derwin K C Chan, Ziyuan Chen, Harrison Hin Sheung Ho, Tsz Him Timothy Tse, Shiu Lun Au Yeung, Shan Luo, Joni H Zhang, Mengyao Wang, Brian Hon-Yin Chung, and Simon J Griffin
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Background: Communication of information about risk of type 2 diabetes (T2D) alone has not been associated with changes in habitual behaviors among individuals of European ancestry. In contrast, the use of wearable devices that monitor physical activity (PA) has been associated with changes in behavior in some studies. It is uncertain whether risk communication might enhance the effects of wearable devices. We aim to assess the effects on wearable-device-measured PA of communicating genetic risk for T2D alone or in combination with goal setting and activity prompts from a wearable device among overweight or obese East Asians. Methods: In a parallel group, randomized controlled trial, a total of 355 overweight or obese East Asian individuals aged 40-60 years will be allocated into one of three groups: 1 control and 2 intervention groups. Blood samples will be used for estimation of T2D genetic risk and analysis of metabolic risk markers. Genetic risk of T2D will be estimated based on 113 SNPs associated with T2D among East Asians using an established method. All three groups will receive a Fitbit device. Both intervention groups will be given T2D genetic risk estimates along with lifestyle advice, but one of the intervention groups will additionally use Fitbit’s step-goal setting and prompt functions. Questionnaires and physical measurements will be administered at baseline, immediately after intervention delivery, and 6 and 12-month post-intervention following standard operating procedures. The primary outcome is time spent in moderate-to-vigorous PA measured through the Fitbit. Secondary outcomes include other parameters of wearable-device-measured PA, sedentary time, and sleep, body mass index, systolic and diastolic blood pressure, five intermediate metabolic risk markers, hand grip strength, self-reported PA, self-reported fruit and vegetable consumption and smoking status, and a list of psychological variables. Discussion: This study will be the first randomized controlled trial using the combination of communication of T2D genetic risk with standard functions of wearable devices in any population. Findings will inform strategies to prevent T2D through lifestyle modification.
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- 2023
16. Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
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Mehul Sharma, Daniel Leung, Mana Momenilandi, Lauren C.W. Jones, Lucia Pacillo, Alyssa E. James, Jill R. Murrell, Selket Delafontaine, Jesmeen Maimaris, Maryam Vaseghi-Shanjani, Kate L. Del Bel, Henry Y. Lu, Gilbert T. Chua, Silvia Di Cesare, Oriol Fornes, Zhongyi Liu, Gigliola Di Matteo, Maggie P. Fu, Donato Amodio, Issan Yee San Tam, Gavin Shueng Wai Chan, Ashish A. Sharma, Joshua Dalmann, Robin van der Lee, Géraldine Blanchard-Rohner, Susan Lin, Quentin Philippot, Phillip A. Richmond, Jessica J. Lee, Allison Matthews, Michael Seear, Alexandra K. Turvey, Rachael L. Philips, Terri F. Brown-Whitehorn, Christopher J. Gray, Kosuke Izumi, James R. Treat, Kathleen H. Wood, Justin Lack, Asya Khleborodova, Julie E. Niemela, Xingtian Yang, Rui Liang, Lin Kui, Christina Sze Man Wong, Grace Wing Kit Poon, Alexander Hoischen, Caspar I. van der Made, Jing Yang, Koon Wing Chan, Jaime Sou Da Rosa Duque, Pamela Pui Wah Lee, Marco Hok Kung Ho, Brian Hon Yin Chung, Huong Thi Minh Le, Wanling Yang, Pejman Rohani, Ali Fouladvand, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Mohammad Miryounesi, Anne Puel, Mohammad Shahrooei, Andrea Finocchi, Paolo Rossi, Beatrice Rivalta, Cristina Cifaldi, Antonio Novelli, Chiara Passarelli, Stefania Arasi, Dominique Bullens, Kate Sauer, Tania Claeys, Catherine M. Biggs, Emma C. Morris, Sergio D. Rosenzweig, John J. O’Shea, Wyeth W. Wasserman, H. Melanie Bedford, Clara D.M. van Karnebeek, Paolo Palma, Siobhan O. Burns, Isabelle Meyts, Jean-Laurent Casanova, Jonathan J. Lyons, Nima Parvaneh, Anh Thi Van Nguyen, Caterina Cancrini, Jennifer Heimall, Hanan Ahmed, Margaret L. McKinnon, Yu Lung Lau, Vivien Béziat, and Stuart E. Turvey
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All institutes and research themes of the Radboud University Medical Center ,Gain of Function Mutation ,Immunology ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Humans ,Immunology and Allergy ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Immunoglobulin E ,STAT6 Transcription Factor ,Asthma ,Food Hypersensitivity - Abstract
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder. ispartof: J Exp Med vol:220 issue:5 pages:e20221755- ispartof: location:United States status: published
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- 2023
17. Clinical implications of mosaicism: a 10-year retrospective review of 83 families in a university-affiliated genetics clinic
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Mianne, Lee, Adrian C Y, Lui, Christopher C Y, Mak, Mandy H Y, Tsang, Jasmine L F, Fung, K S, Yeung, and Brian Hon Yin, Chung
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Universities ,Mosaicism ,Pregnancy ,Karyotyping ,Pediatrics, Perinatology and Child Health ,Humans ,Female ,Genetic Testing ,General Medicine ,Anatomy ,Genetics (clinical) ,Retrospective Studies ,Pathology and Forensic Medicine - Abstract
Mosaicism refers to the coexistence of two or more genetically distinct cell populations in an individual from a single fertilized egg. We performed a retrospective analysis of all patients diagnosed with mosaic disorders between 2010 and 2021 in a university-affiliated genetics clinic, which attends to territory-wide genetic consultations. All patients with confirmed mosaic diagnoses through reproductive (n = 6), prenatal (n = 24), and postnatal (n = 53) testing were examined. We observed that mosaic 45, X (n = 31) and PIK3CA-related overgrowth spectrum (n = 16) disorders were among the most prevalent diagnoses in the clinic, and the total percentage of patients with mosaicism in our cohort was 2.0% (83/4157). A review of the diagnostic journey highlights the challenge in diagnosing mosaic disorders, whereby 38% of the subjects required more than one test sample, and 52% of the cases required more than one orthogonal method of detection to reach the correct diagnosis. While detection of mosaicism is passive through routine clinical testing, for example karyotyping in reproductive and prenatal care, in postnatal care, clinicians can more actively drive the detection of mosaicism. Therefore, we recommend a low threshold for additional genetic testing in suspected mosaicism for more accurate diagnosis and counselling.
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- 2022
18. Successful transition from insulin to sulphonylurea in a child with neonatal diabetes mellitus diagnosed beyond six months of age due to C42R mutation in the KCNJ11 gene
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Sarah Wing-yiu Poon, Brian Hon-yin Chung, Mandy Ho-yin Tsang, and Joanna Yuet-ling Tung
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Pediatrics, Perinatology and Child Health - Published
- 2022
19. PO-03-148 WHOLE GENOME SEQUENCING IN PEDIATRIC CHANNELOPATHY AND CARDIOMYOPATHY
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Sit-Yee Kwok, Julia Z. Shi, Anna K. Kwong, Fong-Ying Shih, Hei To Leung, Mianne Lee, Christopher Mak, Martin Chui, Robin H. Chen, Kin-Shing Lun, Tak-Cheung Yung, Sabrina S. Tsao, and Brian Hon-Yin Chung
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2023
20. Elements of morphology:Standard terminology for the trunk and limbs
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Leslie G. Biesecker, Margaret P. Adam, Brian Hon‐Yin Chung, Kenjiro Kosaki, Leonie A. Menke, Susan M. White, John C. Carey, Raoul C. M. Hennekam, Pediatrics, General Paediatrics, ANS - Cellular & Molecular Mechanisms, ANS - Complex Trait Genetics, ARD - Amsterdam Reproduction and Development, and APH - Quality of Care
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anatomy ,Consensus ,Phenotype ,classification ,Anthropometry ,Genetics ,Humans ,dysmorphology ,nomenclature ,Extremities ,elements of morphology ,Genetics (clinical) - Abstract
An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Additional discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the trunk and limbs and define and illustrate the terms that describe the major characteristics of these body regions.
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- 2022
21. Implementation of Public Funded Genome Sequencing in Evaluation of Fetal Structural Anomalies
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Po Lam So, Annie Shuk Yi Hui, Teresa Wei Ling Ma, Wendy Shu, Amelia Pui Wah Hui, Choi Wah Kong, Tsz Kin Lo, Amanda Nim Chi Kan, Elaine Yee Ling Kan, Shuk Ching Chong, Brian Hon Yin Chung, Ho Ming Luk, Kwong Wai Choy, Anita Sik Yau Kan, and Wing Cheong Leung
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Fetus ,Pregnancy ,Prenatal Diagnosis ,Exome Sequencing ,Genetics ,Humans ,Female ,fetal structural anomalies ,genome sequencing ,diagnostic yield ,clinical impact ,Genetics (clinical) ,Ultrasonography, Prenatal ,Retrospective Studies - Abstract
With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year. We established a web-based multidisciplinary team to facilitate case selection among the expert members. We retrospectively analyzed the fetal phenotypes, test results, turnaround time and clinical impact in the first 15 whole exome sequencing and 14 whole genome sequencing. Overall, the molecular diagnostic rate was 37.9% (11/29). De novo autosomal dominant disorders accounted for 72.7% (8/11), inherited autosomal recessive disorders for 18.2% (2/11), and inherited X-linked disorders for 9.1% (1/11). The median turnaround time for ongoing pregnancy was 19.5 days (range, 13–31 days). Our study showed an overall clinical impact of 55.2% (16/29), which influenced reproductive decision-making in four cases, guided perinatal management in two cases and helped future family planning in ten cases. In conclusion, our findings support the important role of genome sequencing services in the prenatal diagnosis of fetal structural anomalies in a population setting. It is important to adopt a multidisciplinary team approach to support the comprehensive genetic service.
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- 2022
22. Editorial: Genetics and mechanism of ciliopathies
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Steven Lim Cho Pei and Brian Hon Yin Chung
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Genetics ,Molecular Medicine ,Genetics (clinical) - Published
- 2022
23. Rare disease emerging as a global public health priority
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Claudia Ching Yan, Chung, Annie Tsz Wai, Chu, and Brian Hon Yin, Chung
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Rare Diseases ,Health Priorities ,Humans ,COVID-19 ,Public Policy ,Public Health - Abstract
The genomics revolution over the past three decades has led to great strides in rare disease (RD) research, which presents a major shift in global policy landscape. While RDs are individually rare, there are common challenges and unmet medical and social needs experienced by the RD population globally. The various disabilities arising from RDs as well as diagnostic and treatment uncertainty were demonstrated to have detrimental influence on the health, psychosocial, and economic aspects of RD families. Despite the collective large number of patients and families affected by RDs internationally, the general lack of public awareness and expertise constraints have neglected and marginalized the RD population in health systems and in health- and social-care policies. The current Coronavirus Disease of 2019 (COVID-19) pandemic has exposed the long-standing and fundamental challenges of the RD population, and has reminded us of the critical need of addressing the systemic inequalities and widespread disparities across populations and jurisdictions. Owing to the commonality in goals between RD movements and universal health coverage targets, the United Nations (UN) has highlighted the importance of recognizing RDs in policies, and has recently adopted the UN Resolution to promote greater integration of RDs in the UN agenda, advancing UN's commitment in achieving the 2030 Sustainable Development Goals of "leav[ing] no one behind." Governments have also started to launch Genome Projects in their respective jurisdictions, aiming to integrate genomic medicine into mainstream healthcare. In this paper, we review the challenges experienced by the RD population, the establishment and adoption of RD policies, and the state of evidence in addressing these challenges from a global perspective. The Hong Kong Genome Project was illustrated as a case study to highlight the role of Genome Projects in enhancing clinical application of genomic medicine for personalized medicine and in improving equity of access and return in global genomics. Through reviewing what has been achieved to date, this paper will provide future directions as RD emerges as a global public health priority, in hopes of moving a step toward a more equitable and inclusive community for the RD population in times of pandemics and beyond.
- Published
- 2022
24. Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations
- Author
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Claudia Ching Yan Chung, Shirley Pik Ying Hue, Nicole Ying Ting Ng, Phoenix Hoi Lam Doong, Hong Kong Genome Project, Annie Tsz Wai Chu, and Brian Hon Yin Chung
- Subjects
Genetics (clinical) - Published
- 2023
25. Genetics and Mechanism of Ciliopathies
- Author
-
Steven L. C. Pei and Brian Hon-Yin Chung
- Published
- 2022
26. Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies—Experience from a Local Prenatal Diagnostic Laboratory
- Author
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Theodora Hei Tung Lai, Leung Kuen Sandy Au, Yuen Ting Eunice Lau, Hei Man Lo, Kelvin Yuen Kwong Chan, Ka Wang Cheung, Teresa Wei Ling Ma, Wing Cheong Leung, Choi Wah Kong, Wendy Shu, Po Lam So, Anna Ka Yee Kwong, Christopher Chun Yu Mak, Mianne Lee, Martin Man Chun Chui, Brian Hon Yin Chung, and Anita Sik Yau Kan
- Subjects
Health Information Management ,Leadership and Management ,Health Policy ,prenatal whole exome sequencing ,prenatal diagnosis ,genetic counselling ,Health Informatics - Abstract
Fetal structural congenital abnormalities (SCAs) complicate 2–3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup.
- Published
- 2022
27. Author response for 'Biallelic TMEM260 variants cause Truncus Arteriosus, with or without renal defects'
- Author
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null Alistair T. Pagnamenta, null Adam Jackson, null Rahat Perveen, null Glenda Beaman, null Gemma Petts, null Asheeta Gupta, null Zerin Hyder, null Brian Hon‐Yin Chung, null Anita Sik‐Yau Kan, null Ka Wang Cheung, null Wilhelmina S. Kerstjens‐Frederikse, null Kristin M. Abbott, null John C. Ambrose, null Prabhu Arumugam, null Roel Bevers, null Marta Bleda, null Freya Boardman‐Pretty, null Christopher R. Boustred, null Helen Brittain, null Mark J. Caulfield, null Georgia C. Chan, null Greg Elgar, null Tom Fowler, null Adam Giess, null Angela Hamblin, null Shirley Henderson, null Tim J. P. Hubbard, null Rob Jackson, null Louise J. Jones, null Dalia Kasperaviciute, null Melis Kayikci, null Athanasios Kousathanas, null Lea Lahnstein, null Sarah E. A. Leigh, null Ivonne U. S. Leong, null Javier F. Lopez, null Fiona Maleady‐Crowe, null Meriel McEntagart, null Federico Minneci, null Loukas Moutsianas, null Michael Mueller, null Nirupa Murugaesu, null Anna C. Need, null Peter O′Donovan, null Chris A. Odhams, null Christine Patch, null Mariana Buongermino Pereira, null Daniel Perez‐Gil, null John Pullinger, null Tahrima Rahim, null Augusto Rendon, null Tim Rogers, null Kevin Savage, null Kushmita Sawant, null Richard H. Scott, null Afshan Siddiq, null Alexander Sieghart, null Samuel C. Smith, null Alona Sosinsky, null Alexander Stuckey, null Mélanie Tanguy, null Ana Lisa Taylor Tavares, null Ellen R. A. Thomas, null Simon R. Thompson, null Arianna Tucci, null Matthew J. Welland, null Eleanor Williams, null Katarzyna Witkowska, null Suzanne M. Wood, null Orly Elpeleg, null Jenny C. Taylor, null Siddharth Banka, null Asaf Ta‐Shma, and null Genomics England Research Consortium
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,medicine ,business ,Truncus arteriosus - Published
- 2021
28. Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese
- Author
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Jeffrey Fong Ting Chau, Mullin Ho Chung Yu, Martin Man Chun Chui, Cyrus Chun Wing Yeung, Aaron Wing Cheung Kwok, Xuehan Zhuang, Ryan Lee, Jasmine Lee Fong Fung, Mianne Lee, Christopher Chun Yu Mak, Nicole Ying Ting Ng, Claudia Ching Yan Chung, Marcus Chun Yin Chan, Mandy Ho Yin Tsang, Joshua Chun Ki Chan, Kelvin Yuen Kwong Chan, Anita Sik Yau Kan, Patrick Ho Yu Chung, Wanling Yang, So Lun Lee, Godfrey Chi Fung Chan, Paul Kwong Hang Tam, Yu Lung Lau, Kit San Yeung, Brian Hon Yin Chung, and Clara Sze Man Tang
- Subjects
Genetics ,Molecular Biology ,Genetics (clinical) - Abstract
Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people.
- Published
- 2021
29. Delineation of molecular findings by whole exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population
- Author
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Mandy Ho-Yin Tsang, Anna Ka-Yee Kwong, Kate Lok-San Chan, Jasmine Lee-Fong Fung, Mullin Ho-Chung Yu, Christopher Chun-Yu Mak, Kit-San Yeung, Richard J.T. Rodenburg, Jam A.M. Smeitink, Rachel Chan, Thomas Tsoi, Joannie Hui, Sheila Suet-Na Wong, Shuk-Mui Tai, Victor Chi-Man Chan, Che-Kwan Ma, Tsiu-Hang Sharon Fung, Shun-Ping Wu, WK Chan, Brian Hon-Yin Chung, and Cheuk-wing Fung
- Abstract
Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs.Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines.Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n=3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC.Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant was a recurrent founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.
- Published
- 2020
30. Actionable secondary findings in 1116 Hong Kong Chinese based on exome sequencing data
- Author
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Mullin Ho Chung, Yu, Christopher Chun Yu, Mak, Jasmine Lee Fong, Fung, Mianne, Lee, Mandy Ho Yin, Tsang, Jeffrey Fong Ting, Chau, Patrick Ho-Yu, Chung, Wanling, Yang, Godfrey Chi Fung, Chan, So Lun, Lee, Yu Lung, Lau, Paul Kwong Hang, Tam, Clara Sze Man, Tang, Kit San, Yeung, and Brian Hon Yin, Chung
- Subjects
Adult ,Male ,China ,Incidental Findings ,Adolescent ,Genome, Human ,Genetic Variation ,Genomics ,Middle Aged ,Young Adult ,Mutation ,Exome Sequencing ,Hong Kong ,Humans ,Exome ,Female ,Genetic Predisposition to Disease ,Genetic Testing ,Child ,Alleles - Abstract
The use of exome and genome sequencing has increased rapidly nowadays. After primary analysis, further analysis can be performed to identify secondary findings that offer medical benefit for patient care. Multiple studies have been performed to evaluate secondary findings in different ethnicities. However, relevant data are limited in Chinese. Here, with the use of a cohort consisted of 1116 Hong Kong Chinese exome sequencing data, we evaluated the secondary findings in the 59 genes recommended by the American College of Medical Genetics and Genomics. Fifteen unique pathogenic or likely pathogenic variants in 17 individuals were identified, representing a frequency of 1.52% in our cohort. Although 20 individuals harboured pathogenic or likely pathogenic variants in recessive conditions, none carried bi-allelic mutations in the same gene. Our finding was in accordance with the estimation from the American College of Medical Genetics and Genomics that about 1% individuals harbour secondary findings.
- Published
- 2020
31. [Standard training and certification of clinical geneticist in the United States]
- Author
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Hong, Li, Brian Hon-Yin, Chung, Wei, Wang, Hongzheng, Dai, and Anne Chun-Hui, Tsai
- Subjects
Certification ,United States - Published
- 2019
32. [Standardization and accreditation of training programs in clinical genetics in the United States]
- Author
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Wei, Wang, Hongzheng, Dai, Brian Hon-Yin, Chung, Hong, Li, and Anne Chun-Hui, Tsai
- Subjects
Genetics ,United States ,Accreditation ,Education - Published
- 2019
33. AB119. Computer-aided facial recognition of Chinese individuals with 22q11.2 deletion-algorithm training using NIH atlas of human malformation syndromes from diverse population
- Author
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Gary Tsz Kin Mok and Brian Hon-Yin Chung
- Subjects
Clinical Genetics ,medicine.medical_specialty ,Physical medicine and rehabilitation ,medicine.anatomical_structure ,Diverse population ,Atlas (anatomy) ,business.industry ,medicine ,Computer-aided ,General Medicine ,business ,Facial recognition system - Published
- 2017
34. Gene-based meta-analysis of genome-wide association study data identifies independent single-nucleotide polymorphisms in ANXA6 as being associated with systemic lupus erythematosus in Asian populations
- Author
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Jing, Zhang, Lu, Zhang, Yan, Zhang, Jing, Yang, Mengbiao, Guo, Liangdan, Sun, Hai-Feng, Pan, Nattiya, Hirankarn, Dingge, Ying, Shuai, Zeng, Tsz Leung, Lee, Chak Sing, Lau, Tak Mao, Chan, Alexander Moon Ho, Leung, Chi Chiu, Mok, Sik Nin, Wong, Ka Wing, Lee, Marco Hok Kung, Ho, Pamela Pui Wah, Lee, Brian Hon-Yin, Chung, Chun Yin, Chong, Raymond Woon Sing, Wong, Mo Yin, Mok, Wilfred Hing Sang, Wong, Kwok Lung, Tong, Niko Kei Chiu, Tse, Xiang-Pei, Li, Yingyos, Avihingsanon, Pornpimol, Rianthavorn, Thavatchai, Deekajorndej, Kanya, Suphapeetiporn, Vorasuk, Shotelersuk, Shirley King Yee, Ying, Samuel Ka Shun, Fung, Wai Ming, Lai, Maria-Mercè, Garcia-Barceló, Stacey S, Cherny, Pak Chung, Sham, Yong, Cui, Sen, Yang, Dong Qing, Ye, Xue-Jun, Zhang, Yu Lung, Lau, and Wanling, Yang
- Subjects
Asian People ,Humans ,Lupus Erythematosus, Systemic ,Genetic Predisposition to Disease ,Annexin A6 ,Polymorphism, Single Nucleotide ,Genetic Association Studies ,Genome-Wide Association Study - Abstract
Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants.Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing.More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously.Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.
- Published
- 2014
35. CHARGE syndrome patient with novel CHD7 mutation presenting with severe laryngomalacia and feeding difficulty.
- Author
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Cheuk Lam Lau, Yuet Yee Chee, Brian Hon Yin Chung, and Ming Sum Rosanna Wong
- Abstract
We report a case of CHARGE syndrome with atypical phenotype and a novel mutation in the CHD7 gene. Laryngomalacia and swallowing difficulties are prominent features in this case. These are commonly found in patients with CHARGE syndrome and are well described in previous studies. However, with the traditional diagnostic criteria, diagnosis is difficult without the presence of coloboma or choanal atresia. Early diagnosis is possible with the aid of clinical genetics. The current diagnostic criteria would need to be broadened with the inclusion of pathogenic CHD7 variant status as a major criterion. Further research on the function of CHD7 gene may also give us more insight on the pathogenic mechanism of various clinical features of CHARGE syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
36. Epistatic interaction between genetic variants in susceptibility gene ETS1 correlates with IL-17 levels in SLE patients
- Author
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Jing, Zhang, Yan, Zhang, Lu, Zhang, Jing, Yang, Dingge, Ying, Shuai, Zeng, Tsz Leung, Lee, Chak Sing, Lau, Tak Mao, Chan, Alexander Moon Ho, Leung, Chi Chiu, Mok, Sik Nin, Wong, Ka Wing, Lee, Marco Hok Kung, Ho, Pamela Pui Wah, Lee, Brian Hon-Yin, Chung, Chun Yin, Chong, Raymond Woon Sing, Wong, Mo Yin, Mok, Wilfred Hing Sang, Wong, Yu Lung, Lau, and Wanling, Yang
- Subjects
Adult ,Adolescent ,Interleukin-17 ,Genetic Variation ,Epistasis, Genetic ,Proto-Oncogene Protein c-ets-1 ,Young Adult ,Haplotypes ,Case-Control Studies ,Odds Ratio ,Prevalence ,Hong Kong ,Humans ,Lupus Erythematosus, Systemic ,Genetic Predisposition to Disease ,Alleles ,Genetic Association Studies - Abstract
T-helper cells that produce IL-17 (Th17 cells) are a subset of CD4(+) T-cells with pathological roles in autoimmune diseases including systemic lupus erythematosus (SLE), and ETS1 is a negative regulator of Th17 cell differentiation. Our previous work on genome-wide association study (GWAS) identified two variants in the ETS1 gene (rs10893872 and rs1128334) as being associated with SLE. However, like many other risk alleles for complex diseases, little is known on how these genetic variants might affect disease pathogenesis. In this study, we examined serum IL-17 levels from 283 SLE cases and observed a significant correlation between risk variants in ETS1 and serum IL-17 concentration in patients, which suggests a potential mechanistic link between these variants and the disease. Furthermore, we found that the two variants act synergistically in influencing IL-17 production, with evidence of significant genetic interaction between them as well as higher correlation between the haplotype formed by the risk alleles and IL-17 level in patient serum. In addition, the correlation between ETS1 variants and IL-17 level seems to be more significant in SLE patients manifesting renal involvement, dsDNA autoantibody production or early-onset.
- Published
- 2012
37. Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder--implications of a copy number variation involving DPP10.
- Author
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Annisa Shui Lam Mak, Annie Ting Gee Chiu, Gordon Ka Chun Leung, Christopher Chun Yu Mak, Yoyo Wing Yiu Chu, Gary Tsz Kin Mok, Wing Fai Tang, Kelvin Yuen Kwong Chan, Mary Hoi Yin Tang, Elizabeth Tak-Kwong Lau Yim, Kin Wai So, Victoria Qinchen Tao, Cheuk Wing Fung, Virginia Chun Nei Wong, Uddin, Mohammed, So Lun Lee, Marshall, Christian R., Scherer, Stephen W., Anita Sik Yau Kan, and Brian Hon Yin Chung
- Subjects
COMPARATIVE genomic hybridization ,AUTISM spectrum disorders ,PUBLIC health - Abstract
Background: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. Methods: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. Results: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. Conclusions: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
38. Prenatal Tobacco Exposure Shortens Telomere Length in Children.
- Author
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Ip, Patrick, Brian Hon Yin Chung, Frederick Ka Wing, Godfrey Chi Fung Chan, Wen Deng, Wilfred Hing Sang Wong, So Lun Lee, Purdy Ying Ting Chan, Dingge Ying, Wai Lap Wong, Keith Tsz Suen Tung, Yu Lung Lau, Chung, Brian Hon Yin, Ho, Frederick Ka Wing, Chan, Godfrey Chi Fung, Deng, Wen, Wong, Wilfred Hing Sang, Lee, So Lun, Chan, Purdy Ying Ting, and Ying, Dingge
- Subjects
- *
PREGNANT women , *WOMEN'S tobacco use , *TELOMERES , *CHILDREN'S health , *DOSE-response relationship in biochemistry , *CELL division , *PASSIVE smoking , *SMOKING , *SOCIAL classes , *CASE-control method , *PRENATAL exposure delayed effects ,TOBACCO & health - Abstract
Introduction: Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association.Methods: This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling.Results: Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood.Conclusions: Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy.Implications: As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
39. Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations.
- Author
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Yan Zhang, Jing Yang, Jing Zhang, Liangdan Sun, Hirankarn, Nattiya, Hai-Feng Pan, Chak Sing Lau, Tak Mao Chan, Tsz Leung Lee, Alexander Moon Ho Leung, Chi Chiu Mok, Lu Zhang, Yongfei Wang, Jiangshan Jane Shen, Sik Nin Wong, Ka Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon-Yin Chung, and Chun Yin Chong
- Subjects
ANTIGENS ,ASIANS ,COMPARATIVE studies ,DISEASE susceptibility ,GENES ,GENETIC polymorphisms ,RESEARCH methodology ,MEDICAL cooperation ,MEMBRANE proteins ,META-analysis ,PROTEINS ,RESEARCH ,SYSTEMIC lupus erythematosus ,EVALUATION research ,CASE-control method ,SEQUENCE analysis ,GENOTYPES - Abstract
Objectives: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility.Methods: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction.Results: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets.Conclusions: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
40. Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus.
- Author
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Yan Zhang, Yong-Fei Wang, Jing Yang, Jing Zhang, Liangdan Sun, Nattiya Hirankarn, Hai-Feng Pan, Chak Sing Lau, Tak Mao Chan, Tsz Leung Lee, Alexander Moon Ho Leung, Chi Chiu Mok, Lu Zhang, Jiangshan Jane Shen, Sik Nin Wong, Ka Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon-Yin Chung, and Chun Yin Chong
- Published
- 2015
- Full Text
- View/download PDF
41. Validation and application of health utilities index in Chinese subjects with down syndrome.
- Author
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Winnie Ka Yan Mok, Wilfred Hing-Sang Wong, Gary Tsz Kin Mok, Yoyo Wing Yiu Chu, Frederick Ka Wing Ho, Chun Bong Chow, Patrick Ip, and Brian Hon-Yin Chung
- Subjects
DOWN syndrome ,HUMAN chromosome abnormalities ,INTELLECTUAL disabilities ,MENTAL health - Abstract
Objectives The objectives of the study were (1) to validate the Chinese version of Health Utilities Index (HUI-Ch); (2) to examine the Health-related Quality of Life (HRQoL) of Chinese subjects with Down syndrome (DS); and (3) to study the impact of chronic health conditions on HRQoL of Chinese with DS. Methods The multiple choice questionnaire for scoring Health Utilities Index Mark 2 (HUI2) and Health Utilities Index Mark 3 (HUI3) was translated and validated. In addition to the HRQoL scores from HUI2 and HUI3, proxy-data on socio-demographics, and 10 common chronic health conditions for people with DS were collected and analyzed. Data analysis involves multiple imputation and multiple regression analysis to predict variations in HRQoL in relation to different factors. Lastly, a gradient interval was constructed on the number of chronic health conditions in relation to HRQoL. Results HUI-Ch was validated according to standard guidelines. People with DS were found to have a lower HRQoL as compared to the general population, with the majority categorized as moderate or severe on the scale. Behavioral and hearing problems on HUI2, and hearing problems on HUI3 were found to be statistically significant predictors of a lower HRQoL score. A significant gradient relationship existed showing when the number of health problems increased, the HRQoL scores decreased. Conclusions HUI-Ch is a valid instrument to assess HRQoL. It can have broad application in Chinese subjects with DS including the study of the impact of different chronic health conditions on their quality of life. The quantifiable nature of HUI-Ch will facilitate longitudinal study on the well-being of subjects with DS and evaluation of effectiveness of intervention programs in the near future. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
42. EFIN: predicting the functional impact of nonsynonymous single nucleotide polymorphisms in human genome.
- Author
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Shuai Zeng, Jing Yang, Brian Hon-Yin Chung, Yu Lung Lau, and Wanling Yang
- Subjects
SINGLE nucleotide polymorphisms ,HUMAN genome ,AMINO acids ,BIOINFORMATICS ,GENETIC code ,TAXONOMY - Abstract
Background Predicting the functional impact of amino acid substitutions (AAS) caused by nonsynonymous single nucleotide polymorphisms (nsSNPs) is becoming increasingly important as more and more novel variants are being discovered. Bioinformatics analysis is essential to predict potentially causal or contributing AAS to human diseases for further analysis, as for each genome, thousands of rare or private AAS exist and only a very small number of which are related to an underlying disease. Existing algorithms in this field still have high false prediction rate and novel development is needed to take full advantage of vast amount of genomic data. Results Here we report a novel algorithm that features two innovative changes: 1. making better use of sequence conservation information by grouping the homologous protein sequences into six blocks according to evolutionary distances to human and evaluating sequence conservation in each block independently, and 2. including as many such homologous sequences as possible in analyses. Random forests are used to evaluate sequence conservation in each block and to predict potential impact of an AAS on protein function. Testing of this algorithm on a comprehensive dataset showed significant improvement on prediction accuracy upon currently widely-used programs. The algorithm and a web-based application tool implementing it, EFIN (Evaluation of Functional Impact of Nonsynonymous SNPs) were made freely available (http://paed.hku.hk/efin/) to the public. Conclusions Grouping homologous sequences into different blocks according to the evolutionary distance of the species to human and evaluating sequence conservation in each group independently significantly improved prediction accuracy. This approach may help us better understand the roles of genetic variants in human disease and health. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
43. A patient with mosaic neurofibromatosis type 2 presenting with early onset meningioma.
- Author
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Yoyo Wing-Yiu Chu, Daniel Ka Leung Cheuk, Brian Hon Yin Chung, Bowers, Naomi L., Shau-Yin Ha, Alan Kwok-Shing Chiang, and Godfrey Chi-Fung Chan
- Published
- 2014
- Full Text
- View/download PDF
44. Whole genome sequencing in paediatric channelopathy and cardiomyopathy
- Author
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Sit Yee Kwok, Anna Ka Yee Kwong, Julia Zhuo Shi, Connie Fong Ying Shih, Mianne Lee, Christopher C. Y. Mak, Martin Chui, Sabrina Tsao, and Brian Hon Yin Chung
- Subjects
channelopathy ,cardiomyopathy ,paediatrics ,genome sequencing ,intronic variants ,MYBPC3 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundPrecision medicine in paediatric cardiac channelopathy and cardiomyopathy has a rapid advancement over the past years. Compared to conventional gene panel and exome-based testing, whole genome sequencing (WGS) offers additional coverage at the promoter, intronic regions and the mitochondrial genome. However, the data on use of WGS to evaluate the genetic cause of these cardiovascular conditions in children and adolescents are limited.MethodsIn a tertiary paediatric cardiology center, we recruited all patients diagnosed with cardiac channelopathy and cardiomyopathy between the ages of 0 and 18 years old, who had negative genetic findings with prior gene panel or exome-based testing. After genetic counselling, blood samples were collected from the subjects and both their parents for WGS analysis.ResultsA total of 31 patients (11 cardiac channelopathy and 20 cardiomyopathy) were recruited. Four intronic splice-site variants were identified in three cardiomyopathy patients, which were not identified in previous whole exome sequencing. These included a pathogenic variant in TAFAZZIN:c.284+5G>A (Barth syndrome), a variant of unknown significance (VUS) in MYBPC3:c.1224-80G>A and 2 compound heterozygous LP variants in LZTR1 (LZTR1:c.1943-256C>T and LZTR1:c1261-3C>G) in a patient with clinical features of RASopathy. There was an additional diagnostic yield of 1.94% using WGS for identification of intronic variants, on top of conventional gene testing.ConclusionWGS plays a role in identifying additional intronic splice-site variants in paediatric patients with isolated cardiomyopathy. With the demonstrated low extra yield of WGS albeit its ability to provide potential clinically important information, WGS should be considered in selected paediatric cases of cardiac channelopathy and cardiomyopathy in a cost-effective manner.
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- 2024
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45. The growing needs of genetic counselling—Feasibility in utilization of tele-genetic counselling in Asia and Hong Kong
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Annie Tsz Wai Chu, Claudia Ching Yan Chung, Shirley Pik Ying Hue, and Brian Hon Yin Chung
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tele-genetics ,tele-genetic counselling ,telemedicine ,genetic counselling ,Hong Kong Genome Project ,Genetics ,QH426-470 - Abstract
The need for the expansion of genomic services has been at a record time high in the past decade. As technological advancement continues to strengthen the entire genetic and genomic pipeline and clinical operational workflow, the major challenge remains to be the speed of workforce development to meet service growth. In particular, the international expansion of genetic counselling (GC) services has been a topic of interest for the past few years. GC is an emerging profession in most of Asia, and in many countries the profession of GC often refers to physicians or front-line health workers with expertise in genetics to provide GC services rather than being a specific independent profession. As genetic and genomic services, especially pre-test and post-test GC, expand globally, the need to tackle the longstanding obstacles of GC personnel shortage and funding issues must not be overlooked. There is an urgent need internationally, and especially in Asia, where GC profession is comparatively less well-established, to seek alternative approaches to meet service demand. The present review examines the global development and feasibility of tele-genetics and tele-genetic counselling (TGC), and serves as the foundation to explore a possible roadmap in Hong Kong via the Hong Kong Genome Project.
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- 2023
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46. IDENTIFICATION OF 7 NOVEL TRANSFORMING GROWTH FACTOR β RECEPTOR 2 MUTATIONS IN CHINESE PATIENTS WITH MARFAN SYNDROME.
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Brian Hon-Yin Chung, Li, Susanna, Lam, Stephen Tak-Sum, Wanling Yang, Kin-Shing Lun, and Yu-Lung Lau
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MARFAN syndrome , *TRANSFORMING growth factors , *GENETIC mutation , *CONNECTIVE tissue diseases , *LIQUID chromatography , *PHENOTYPES - Abstract
INTRODUCTION: Marfan syndrome (MFS) (Online Mendelian Inheritance in Man [OMIM] No. 154700) is an autosomal-dominant connective tissue disorder that affects multiple systems including the cardiovascular, ocular, and musculoskeletal systems. Fibrillin 1 (FBN1) (OMIM No. 134797) mutations are causative in >90% of the cases, and recent studies have shown that transforming growth factor β receptor 2 (TGFBR2) (OMIM No. 190182) mutations could be identified in ~10% of non-FBN1 probands (Mátyás G, Arnold E, Carrel T, et al. Hum Mutat. 2006;27:760-769). OBJECTIVE: Our objective was to examine the mutation spectrum of TGFBR2 in non-FBN1 Chinese patients with MFS and related phenotypes. METHODS: All Chinese probands who were referred for evaluation of MFS and tested negative for FBN1 mutations were included. Mutational screening was performed by denaturing high-pressure liquid chromatography (Kosaki K, Udaka T, Okuyama T. Mol Genet Metab. 2005;86:117-123). Amplicons with an abnormal elution pattern were selected for direct sequencing. RESULTS: Seven novel mutations were identified in 7 of 41 probands. All of them had prominent cardioskeletal phenotypes without ocular or dural involvement, which confirmed previous findings (Disabella E, Grasso M, Marziliano N, et al: Eur J Hum Genet. 2006; 14;34-38). Six mutations were missense (R190H, D247V, T325P, G357R, I510N, and T530I), and 1 was frameshift (P501fsX17). Except for R190H, all were found in the functionally important kinase domain. Bioinformatic analyses showed that (1) all mutations occurred in conserved positions by cross-species comparison between 6 orthologs, and (2) R190H, T325P, T530I, and G357R were also found in conserved positions among 3 paralogs (TGFBRI and activin receptors AVR2A and AVR2B) in the TGFBR superfamily. None of the 7 were found in 50 unaffected individuals (100 normal alleles). With the TGFBR2 mutations, 4 additional probands would fulfill the diagnostic criteria of MFS. CONCLUSIONS: TGFBR2 mutation was identified in 17% of our non-FBN1 probands. It should be considered in the evaluation for MFS after FBNI screening, especially if there are compatible clinical features [ABSTRACT FROM AUTHOR]
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- 2008
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47. Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese
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Jeffrey Fong Ting Chau, Mullin Ho Chung Yu, Martin Man Chun Chui, Cyrus Chun Wing Yeung, Aaron Wing Cheung Kwok, Xuehan Zhuang, Ryan Lee, Jasmine Lee Fong Fung, Mianne Lee, Christopher Chun Yu Mak, Nicole Ying Ting Ng, Claudia Ching Yan Chung, Marcus Chun Yin Chan, Mandy Ho Yin Tsang, Joshua Chun Ki Chan, Kelvin Yuen Kwong Chan, Anita Sik Yau Kan, Patrick Ho Yu Chung, Wanling Yang, So Lun Lee, Godfrey Chi Fung Chan, Paul Kwong Hang Tam, Yu Lung Lau, Kit San Yeung, Brian Hon Yin Chung, and Clara Sze Man Tang
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people.
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- 2022
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48. Hospital mortality in patients with rare diseases during pandemics: lessons learnt from the COVID-19 and SARS pandemics
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Claudia Ching Yan Chung, Wilfred Hing Sang Wong, and Brian Hon Yin Chung
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Rare disease ,Pandemic ,COVID-19 ,SARS ,Hong Kong ,Mortality ,Medicine - Abstract
Abstract Background The threat and experience of pandemics occur differently for different groups. The rare disease population is at particular risk of being further marginalised during pandemics. In this study, our objective was to assess the hospital mortality patterns in the rare disease and the general populations during the coronavirus disease of 2019 (COVID-19) and severe acute respiratory syndrome (SARS) pandemics in Hong Kong. Methods All admission records during the COVID-19 pandemic (January 23–August 23, 2020) and SARS pandemic (March 11–June 30, 2003) were extracted from the local public healthcare database. Patients with rare diseases were identified using one or more of the 1084 10th version International Classification of Diseases and Related Health Problems (ICD-10) codes cross-referenced with 467 ORPHAcodes. Hospital mortality patterns were compared in patients with and without COVID-19/SARS infection. Admission records during the same period in 2019 and 2002 were retrieved for comparison. Results During the COVID-19 pandemic, 407,219 patients were admitted to one or more of the 43 public hospitals in Hong Kong, of which, 13,894 were patients with rare diseases (3.4%). A total of 4381 and 77 patients from the general and rare disease populations were infected with COVID-19. Rare disease patients had an adjusted 3.4 times odds of COVID-19-related hospital mortality compared with that of the general population (95% C.I. 1.24–9.41). COVID-19-related mortality was almost exclusively seen in patients ≥ 60 years. While age-related increase in mortality was also observed for the general population during the SARS pandemic, the pattern observed in the rare disease population was significantly different, with a 12.5 times higher SARS-related mortality observed in rare disease patients ≤ 18 years than those in the general population (12.5% vs 1.0%). Patients admitted during the same pandemic periods without coronavirus infection had a significantly higher hospital mortality compared with those admitted one year before the pandemic (p
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- 2021
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49. Perception of personalized medicine, pharmacogenomics, and genetic testing among undergraduates in Hong Kong
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Nicholas Yan Chai Cheung, Jasmine Lee Fong Fung, Yvette Nga Chung Ng, Wilfred Hing Sang Wong, Claudia Ching Yan Chung, Christopher Chun Yu Mak, and Brian Hon Yin Chung
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Education ,Ethical ,Legal and Social Implications ,Genetic testing ,Personalized medicine ,Pharmacogenomics ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI). Results The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6–14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0–6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM. When asked about their perceptions on GT, 60% rated their genetic knowledge as “School Biology” level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on “Patient Privacy” (80%) and “Data Confidentiality” (68%). Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel “helpless or pessimistic” (56%), “inadequate or different” (59%), and “disadvantaged at job seeking” (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1–3.5), compared to younger undergraduates. Conclusion Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.
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- 2021
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50. A thematic study: impact of COVID-19 pandemic on rare disease organisations and patients across ten jurisdictions in the Asia Pacific region
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Claudia Ching Yan Chung, Yvette Nga Chung Ng, Ritu Jain, and Brian Hon Yin Chung
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COVID-19 ,Rare disease ,Rare disease organisation ,Rare disease patients ,Asia Pacific ,Thematic analysis ,Medicine - Abstract
Abstract Background This study assesses the areas and extent of impact of the Coronavirus Disease of 2019 (COVID-19) pandemic on rare disease (RD) organisations in the Asia Pacific region. There is no existing literature that focuses on such impact on RD organisations in any jurisdictions, nor RD populations across multiple jurisdictions in the Asia Pacific region. A cross-sectional survey was distributed to RD organisations between April and May 2020. Quantitative and qualitative data on the impact of COVID-19 on RD organisations and patients were collected from the organisation representative’s perspective. Qualitative data was analysed using thematic analysis. A follow-up focus group meeting was conducted in August 2020 to validate the survey findings and to discuss specific needs, support and recommendations for sustainable healthcare systems during the pandemic. Results A total of 80 RD organisations from Australia, Hong Kong Special Administrative Region of China, India, Japan, mainland China, Malaysia, New Zealand, the Philippines, Singapore and Taiwan participated in the study. Of all, 89% were concerned about the impact of pandemic on their organisations. Results indicate that 63% of the organisations functioned at a reduced capacity and 42% stated a decrease in funding as their biggest challenge. Overall, 95% believed their patients were impacted, particularly in healthcare access, social lives, physical health, psychological health and financial impact. Specifically, 43% identified the reduced healthcare access as their top impact, followed by 26% about the impact on daily living and social life. Focus group meeting discussed differential impact across jurisdictions and point towards telemedicine and digitalisation as potential solutions. Conclusions This serves as the first study to assess the impact of COVID-19 on RD patients and organisations across multiple jurisdictions in the Asia Pacific region, identifying major themes on the impact on both RD patients and organisations. By including 80 organisations from ten jurisdictions, our study presents the most comprehensive assessment of the pandemic’s impact to date. It highlights the need for mental health support and sheds light on moving towards telemedicine and digitalisation of organisation operation, which constitutes a sustainable model in times of pandemics and beyond.
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- 2021
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