Expanded carrier screening using next-generation sequencing of 123 Hong Kong Chinese families: a pilot study.

INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.

A scoping review of sexual transmission related HIV research among key populations in Malaysia: Implications for interventions across the HIV care cascade.

The Malaysian government has committed to 'Fast Tracking the HIV Response' to achieve UNAIDS 2030 targets to end AIDS. The epidemic is concentrated among key populations and has shifted from people who inject drugs to HIV infection through sexual transmission among men who have sex with men, sex workers and transgender people. The aim of this scoping review was to examine social and behavioural research published since 2005 that can inform understanding of each stage of the 90:90:90 treatment cascade (as proposed by UNAIDS), including HIV risk behaviours and testing practices that precede entry. We found a concentration of studies related to predictors or correlates of HIV infections (mostly among men who have sex with men) and a shortfall in literature pertaining to sex workers or transgender people. While several studies examined factors associated with HIV testing, only one examined uptake of antiretroviral therapy and two explored issues of treatment adherence. No study examined broader care and support of people living with HIV. To scale-up effective programmes and apprise investment to achieve the ambitious targets set-out in the Malaysian National HIV/AIDS Strategic Plan, a combination of comprehensive strategic information and evidence generated through primary research is critical.

Molecular and clinical characterization of citrin deficiency in a cohort of Chinese patients in Hong Kong.

BACKGROUND AND OBJECTIVES: This retrospective study analysed a case series of subjects with citrin deficiency, and aims to present the molecular and clinical characterization of this disease in the Hong Kong Chinese population for the first time. PATIENTS AND METHODS: Data from medical records of eighteen patients with citrin deficiency (years 2006-2015) were retrieved. Demographic data, biochemical parameters, radiological results, genetic testing results, management, and clinical outcome were collected and analysed. RESULTS: Eighteen patients with diagnosis of citrin deficiency were recruited. All 18 patients carried at least one common pathogenic variant c.852_855delTATG in SLC25A13. Prolonged jaundice (neonatal intrahepatic cholestasis caused by citrin deficiency, NICCD) was the most common presenting symptom, in conjunction with elevated plasma citrulline, threonine, alkaline phosphatase, and alpha-fetoprotein levels. The abnormal biochemical parameters including liver derangement returned to normal range in most of the cases by 6 months of age after the introduction of a lactose-free formula. There were a few cases with atypical presentations. Two subjects did not present with NICCD, and were subsequently diagnosed later in life after their siblings presented with symptoms of citrin deficiency at one month of age and subsequently received a molecular diagnosis. One patient with citrin deficiency also exhibited multiple liver hemangioendotheliomas, which subsided gradually after introduction of a lactose-free formula. Only one patient from this cohort was offered expanded metabolic screening at birth. She was not ascertained by conducted newborn screening and was diagnosed upon presentation with cholestatic jaundice by 1 month of age. CONCLUSION: This is the first report of the clinical and molecular characterization of a large cohort of patients with citrin deficiency in Hong Kong. The presentation of this cohort of patients expands the clinical phenotypic spectrum of NICCD. Benign liver tumors such as hemangioendotheliomas may be associated with citrin deficiency in addition to the well-known association with hepatocellular carcinoma. Citrin deficiency may manifest in later infancy period with an NICCD-like phenotype. Furthermore, this condition is not always ascertained by expanded newborn metabolic screening testing.

Expanded newborn metabolic screening programme in Hong Kong: a three-year journey.

INTRODUCTION: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. METHODS: We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. RESULTS: During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. CONCLUSION: The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.

Headache diagnosis, disability and co-morbidities in a multi-ethnic, heterogeneous paediatric Asian population.

This was a questionnaire survey on headache and migraine prevalence in 2873 Singaporean schoolchildren aged 6 to 16 years. ICHD-II headache classification, disability assessment with PedMIDAS and screening of psychosocial co-morbidities with the Paediatric Symptom Checklist were conducted. Lifetime headache prevalence was high at 80.6%, migraine prevalence was 8.6% and tension headache prevalence was 10.0%. Headache and migraine prevalence was high compared with that found in other Asian studies. Factors significantly associated with headache included adolescent age (OR = 1.5 [95% CI 1.3-1.9], p < .001), female gender at primary (OR = 1.4 [95% CI 1.1-1.8], p = .003) and secondary (OR = 1.8 [95% CI 1.3-2.5], p < .001) levels and Malay ethnicity at the primary level (OR = 2.8 [95% CI 1.6-4.9], p < .001). The average PedMIDAS score for headache disability was 3.2 +/- 8.4, and migraine disability (PedMIDAS 8.1 +/- 11.2-15.2 +/- 29.6) was lower than in some studies. Self-medication (20.5%) and use of alternative therapy (59.0%) were high among chronic daily headache sufferers. Routine sleep and stress screening is recommended for children with headaches. Recognition of the influence of genetics, lifestyle and cultural factors on headache management should be emphasized.

Biomimetic processing of bioactive interface on silicon substrates.

To facilitate the implantation of silicon-based devices in vivo, the presence of a biocompatible and bioactive coating is noted to be an essential factor. The objective of this present work is therefore to explore a relatively simple and low cost process to induce the formation of bioactive apatite on silicon. The formation of apatite on silicon was carried out by a biomimetic approach on two orientations of silicon wafer, namely (100) and (111). The samples are functionalized by chemical etching, followed by incubation in a simulated body fluid. Scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction analysis, and X-ray photoelectron spectroscopy were carried out. It was found that the growth of apatite is dependent on the orientation of the silicon wafer. Cell culturing experiment further verified the biological performance of the apatite-coated silicon samples.

Preschool children's difficulty understanding the types of information obtained through the five senses.

Two studies explored 3- and 4-year-olds' (N = 60) understanding that the five senses can each lead to different types of knowledge. In Study 1, 40 children engaged in five scenarios in which they could only perform one sensory action to identify the property of an object (e.g., color, scent). After performing the action, children were asked how they found out the property and to show the experimenter how they had found it out. Using a Mr. Potato Head doll, children were also asked to indicate the sensory organ the doll would need to use to identify the property. In Study 2, 20 children presented with five Mr. Potato Head dolls, each sporting only one sensory organ (e.g., a nose), were asked which Mr. Potato Head could find out the property in question. The 3-year-olds performed significantly poorer than the 4-year-olds on all tasks, suggesting a marked transition in children's ability to recognize the origin of their modality-specific knowledge during the time period between 3 and 4 years of age.