A5016149539- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Mitochondrial Function and Pathology
- Genetic factors in colorectal cancer
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Single-cell and spatial transcriptomics
- Cystic Fibrosis Research Advances
- Genomics and Phylogenetic Studies
- Genetic Neurodegenerative Diseases
- Congenital Heart Disease Studies
- Muscle Physiology and Disorders
- Prenatal Screening and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Machine Learning in Bioinformatics
- Congenital Ear and Nasal Anomalies
- Hemoglobinopathies and Related Disorders
- Berberine and alkaloids research
- Head and Neck Surgical Oncology
- Genetic and Kidney Cyst Diseases
- Coenzyme Q10 studies and effects
- Craniofacial Disorders and Treatments
University of Hong Kong
2017-2023
Chinese University of Hong Kong
2020-2023
Duchess of Kent Children's Hospital
2018-2022
Queen Mary Hospital
2017-2020
Exome sequencing (ES) has become one of the important diagnostic tools in clinical genetics with a reported rate 25-58%. Many studies have illustrated and immediate impact ES. However, up to 75% individuals remain undiagnosed there is scarce evidence supporting utility beyond follow-up period >1 year. This 3-year analysis our previous publication by Mak et al. (NPJ Genom. Med. 3:19, 2018), evaluate long-term ES potential exome reanalysis. The yield initial study was 41% (43/104). reanalysis...
Rapid whole-exome sequencing (rWES) offers the potential for early diagnosis-predicated precision medicine. Previous evidence focused predominantly on infants from intensive care unit (ICU). This study sought to examine diagnostic and clinical utility, economic impact management of rWES in patients beyond infancy ICU setting.rWES was performed a prospective cohort with suspected monogenic disorder referred territory-wide paediatric ICUs non-ICUs Hong Kong urging rapid genetic diagnosis. All...
MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing have been reported individuals with variable neurodevelopmental anomalies non-specific facial features. We identified cluster de novo truncating mutations cohort 23 strikingly similar dysmorphic features, especially midface hypoplasia, intellectual disability severe expressive language delay. Imaging...
ABSTRACT Individuals with autism spectrum disorder (ASD) or related neurodevelopmental disorders (NDDs) often carry disruptive mutations in genes that are depleted of functional variation the broader population. We build upon this observation and exome sequencing from 154,842 individuals to explore allelic diversity rare protein-coding contributing risk for ASD NDDs. Using an integrative statistical model, we jointly analyzed protein-truncating variants (PTVs), damaging missense variants,...
Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it not been widely adopted the prenatal setting. This study evaluated use of WES fetuses with structural congenital anomalies (SCAs) detected on ultrasound. Thirty-three families fetal SCAs ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various samples including amniotic fluid, chorionic villi, placental tissue. Parental...
Okur‐Chung syndrome is a neurodevelopmental condition attributed to germline CSNK2A1 pathogenic missense variants. We present 8 unreported subjects with the above syndrome, who have recognizable dysmorphism, varying degrees of developmental delay and multisystem involvement. Together 6 previously reported cases, we case series 7 female male subjects, highlighting facial features (microcephaly, hypertelorism, epicanthic fold, ptosis, arched eyebrows, low set ears, ear fold abnormality, broad...
Abstract Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4 . Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed mutations. Five them have classical neonatal-onset encephalo-cardiomyopathy, while others infantile onset more heterogeneous clinical presentations. We also identify founder mutation (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting higher chance occurrence...
Early onset drug-resistant epilepsy is a neurologic disorder in which 2 antiepileptic drugs fail to maintain the seizure-free status of patient. Heterogeneous clinical presentations make diagnosis challenging. We aim identify underlying genetic causes pediatric cohort with and evaluate whether findings can provide information on patient management.We include patients before 18 years age. Singleton chromosomal microarray (CMA) followed by whole exome sequencing (WES) was performed using...
Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in Chinese population is limited lack of population-wide data. In this study, secondary analysis exome sequencing data was conducted study pharmacogenomics 1116 Hong Kong Chinese. We aimed identify spectrum actionable variants and rare, predicted deleterious that are potentially Chinese, estimate proportion dispensed drugs may...
Abstract RASopathies are a group of heterogeneous conditions caused by germline mutations in RAS/MAPK signalling pathway genes. With next-generation sequencing (NGS), capacity is no longer limitation to molecular diagnosis. Instead, the rising number variants unknown significance (VUSs) poses challenges clinical interpretation and genetic counselling. We investigated potential an integrated pipeline combining NGS functional assessment for diagnosis RASopathies. included 63 Chinese patients...
Traditional carrier screening has been utilized for the detection of carriers genetic disorders. Since a comprehensive assessment frequencies recessive conditions in Southern Chinese population is not yet available, we performed secondary analysis on spectrum and status 315 genes causing autosomal disorders 1543 individuals with next-generation sequencing data, 1116 exome 427 genome data. Our data revealed that 1 2 people (47.8% population) was one or more conditions, 12 (8.30% treatable...
Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with broad spectrum overlapping the clinical presentations that makes diagnosis challenging. Notably, recent introduction whole-exome sequencing (WES) is introducing rapid changes on NMDs. We aimed to investigate diagnostic value WES for pediatric-onset NMDs.We applied integrated approach and performed in 50 Chinese subjects (30 males, 20 females) undiagnosed NMDs despite previous specific tests. The patients...
Background In nonsyndromic conotruncal cardiac defects, the use of next-generation sequencing for clinical diagnosis is increasingly adopted, but gene-disease associations in research are only partially translated to diagnostic panels, suggesting a need evidence-based consensus. Methods and Results an exome data set 245 patients with we performed burden analysis on high-confidence congenital heart disease gene list (n=132) rare (<0.01%) ultrarare (absent Genome Aggregation Database)...
Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms myopathy. The c.1516A>C variant has recently been reported as a founder mutation southern Chinese.We report six cases 8 involves variant, from five unrelated families non-consanguineous Chinese. pre- and postnatal phenotypes these were reviewed with emphasis on prenatal clinical features. Genetic testing for was performed three patients homozygous mutations.Common...
Abstract Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed our paediatric-onset MD cohort Southern Chinese origin, with aim identifying key disease-causing variants patients MDs. Methods We recruited who had...
Human heterotaxy is a group of congenital disorders characterized by misplacement one or more organs according to the left-right axis. The genetic causes human are highly heterogeneous.We performed exome sequencing in cohort 26 probands with followed gene burden analysis for enrichment novel rare damaging mutations. Transcription activator-like effector nuclease was used generate somatic loss-of-function mutants zebrafish model. Ciliary defects were examined whole-mount immunostaining...
Aim: The Hong Kong Genome Project (HKGP) is the first large-scale genome sequencing (GS) project in Special Administrative Region. Institute (HKGI) entrusted with task of implementing HKGP. With aim to sequence 45,000-50,000 genomes five years, it project’s goal provide participants more precise diagnosis and personalised treatment, drive application integration genomic medicine into routine clinical care. Methods: HKGI Laboratory’s hardware software components were customised tailor needs...
Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a segment without visible gain loss genetic material. BCAs occur at frequency 1 500 newborns and associated with an increased risk multiple congenital anomalies and/or neurodevelopmental disorders, especially if it is de novo mutation. In this pilot project, we used short read genome sequencing (GS) to retrospectively re-sequence ten prenatal subjects compared performance GS original karyotyping....
Bronchiectasis is the abnormal dilation of airway which may be caused by various etiologies in children. Beyond more recognized cause bacterial and viral infections primary immunodeficiencies, other genetic conditions such as cystic fibrosis ciliary dyskinesia (PCD) can also contribute to disease. Currently, there still debate on whether genome sequencing (GS) or exome reanalysis (rES) would beneficial if initial targeted testing results returned negative. This study aims provide a...
<h3>Background</h3> Pharmacogenetics is the study of variability in drug response caused by genetic variations. It estimated that over two million hospitalized patients develop severe adverse reactions United States annually, incurring a direct medical cost 200 billion US dollars (USD). This indicates huge potential reducing healthcare costs even if only small proportion are preventable genotype-guided prescription. The current clinical applications pharmacogenetics mostly limited to...
Abstract BackgroundMitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed our paediatric-onset MD cohort Southern Chinese origin, with aim identifying key disease-causing variants patients MDs.MethodsWe recruited who had...