Socioeconomic Gradient in Childhood Obesity and Hypertension: A Multilevel Population-Based Study in a Chinese Community

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Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis

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The clinical impact of chromosomal microarray on paediatric care in Hong Kong

Objective To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong. Methods We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their “clinical actionability” based on established criteria. Results Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p<0.001). Nineteen out of the 28 management recommendations are “evidence-based” on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12). Conclusion The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.published_or_final_versio

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

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The genetics of macrocephaly, autistic spectrum disorders and developmental delay in Chinese children

Poster PresentationsObjective: Macrocephaly is a common dysmorphic feature in children with autistic spectrum disorders and developmental problems. Previous studies showed that 14–34% of autistic children had head circumference >97 percentile. The aim of this study was to investigate the genetic causes of children with macrocephaly, autistic spectrum disorders and/ or global developmental delay. Method: Chinese children diagnosed with macrocephaly with head circumference >2 S.D. with either autistic spectrum disorders and/ or global developmental delay were recruited prospectively from 1st January 2010 to 31st December 2014. After obtaining informed consent, whole exome sequencing was done on the patients’ blood and buccal DNA. There were total of 18 patients and 27 family members. Coding exons in DNA samples from the patients and the family members were captured by Illumina Truseq Exome Enrichment Kit (64mb) and sequenced by Illumina Hiseq 2000 machine. The whole sequencing data analysis follows the best practice of GATK 3.2 (The Genome Analysis Toolkit, Broad Institute). Results: Out of the 18 patients with macrocephaly, autistic spectrum and/ or global developmental delay, 5 patients (27%) were identified to have genetic mutations (3 de novo mutations, 1 autosomal dominant and 1 was X-linked inherited). 4 out of the 5 mutations were linked to the PI3KAKT- mTOR pathway. Interestingly, one of these patients with biallelic PTEN mutations had the most severe clinical features of macrocephaly, global developmental delay and early death. Conclusion: Children with macrocephaly, autistic spectrum disorders and/ or global developmental delay should be offered genetic evaluations to rule out megalencephaly syndromes related to the PI3K-AKT-mTOR pathway. Early recognition will help to identify and treat complications such as increased cancer risks and early lethality