Normative data and psychometric properties of the Connor–Davidson Resilience Scale (CD-RISC) and the abbreviated version (CD-RISC2) among the general population in Hong Kong

postprin

Direct participation in and indirect exposure to the occupy central movement and depressive symptoms: a longitudinal study of Hong Kong adults

postprin

Clinical application of whole exome sequencing for paediatric undiagnosed diseases in Hong Kong: experience from first sixty cases

Oral Free Paper Session: Oral Presentation 5published_or_final_versio

A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update

De novo germline mutations in HRAS cause Costello syndrome, with >95% of the mutations causing Costello syndrome affecting amino acid position 12 (p.Gly12) or 13 (p.Gly13). We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G > C:p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in <1% of patients with Costello syndrome. From literature search, there were only two other patients reported with mutations involving the same location. We summarized and updated their findings, and discussed evidence to show that these patients with less obvious signs of Costello syndrome may not necessarily run a more benign clinical course.postprin

Whole-Genome Array CGH Evaluation for Replacing Prenatal Karyotyping in Hong Kong

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De novo large rare copy-number variations contribute to conotruncal heart disease in Chinese patients

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Homozygous Missense Mutation in ABR Causes Cerebellar Hypoplasia with Early Lethality - A New Condition Identified by Exome Sequencing?

Poster PresentationWe performed whole exome sequencing (WES) in a consanguineous Pakistani family with a recurrent pattern of cerebellar hyposplasia, intra-uterine growth restriction, and various CNS/non-CNS malformations, resulting in early lethality (1 perinatal death and 1 intrauterine death). Karyotype (in the first pregnancy) and oligonucleotide array (in the 2nd affected pregnancy) were normal. Parents declined post-mortem examination. By WES, a novel homozygous missense mutation was identified in the ABR gene (ABR: NM_021962.4:c.G2455T: p.A819S) in both affected pregnancies. Both parents were identified to be heterozygous of the same mutation while the healthy child did not carry any mutation. The mutation is located in a highly conserved region and is predicted to be highly damaging by all the commonly used in silico mutation prediction tools. The protein encoded by ABR gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Previous reports showed that OPHN1, mutations in which cause X-linked mental retardation with cerebellar hypoplasia (OMIM300486), also encodes for a regulator of GTPase-activating protein. Both OPHN1 and ABR are highly expressed in the human brain especially in the cerebellum, and both contain a GTPase-activating domain. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Other studies have demonstrated a regulatory role of Rho GTPase in differentiation of cerebellar neurons, and that ethanolassociated impairment of Rho GTPase might contribute to brain defects in fetal alcohol syndrome. Further functional studies, including zebrafish morpholino studies, are currently ongoing. WES can be helpful in individual families with undiagnosed lethal MCA syndromes to identify potentially responsible autosomal recessive mutations and may lead to a better understanding of the role of various developmental pathways in human embryogenesis.published_or_final_versio

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

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

Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism

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Mutation in PIK3CA leading to developmental mosaic disorders

Oral Free Paper Session: Oral Presentation 8published_or_final_versio