| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Boyle, Breidge, et al.
(författare)
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Estimating Global Burden of Disease due to congenital anomaly : An analysis of European data
- 2018
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Ingår i: Archives of Disease in Childhood: Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 103:1, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective To validate the estimates of Global Burden of Disease (GBD) due to congenital anomaly for Europe by comparing infant mortality data collected by EUROCAT registries with the WHO Mortality Database, and by assessing the significance of stillbirths and terminations of pregnancy for fetal anomaly (TOPFA) in the interpretation of infant mortality statistics. Design, setting and outcome measures EUROCAT is a network of congenital anomaly registries collecting data on live births, fetal deaths from 20 weeks' gestation and TOPFA. Data from 29 registries in 19 countries were analysed for 2005-2009, and infant mortality (deaths of live births at age <1 year) compared with the WHO Mortality Database. Eight EUROCAT countries were excluded from further analysis on the basis that this comparison showed poor ascertainment of survival status. Results According to WHO, 17%-42% of infant mortality was attributed to congenital anomaly. In 11 EUROCAT countries, average infant mortality with congenital anomaly was 1.1 per 1000 births, with higher rates where TOPFA is illegal (Malta 3.0, Ireland 2.1). The rate of stillbirths with congenital anomaly was 0.6 per 1000. The average TOPFA prevalence was 4.6 per 1000, nearly three times more prevalent than stillbirths and infant deaths combined. TOPFA also impacted on the prevalence of postneonatal survivors with non-lethal congenital anomaly. Conclusions By excluding TOPFA and stillbirths from GBD years of life lost (YLL) estimates, GBD underestimates the burden of disease due to congenital anomaly, and thus declining YLL over time may obscure lack of progress in primary, secondary and tertiary prevention.
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| 3. |
- Greenlees, Ruth, et al.
(författare)
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Paper 6: EUROCAT Member Registries: Organization and Activities
- 2011
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Ingår i: Birth Defects Research Part C: Embryo Today: Reviews. - : Wiley. - 1542-975X. ; 91:Suppl. 1, s. 51-100
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: EUROCAT is a network of population-based congenital anomaly registries providing standardized epidemiologic information on congenital anomalies in Europe. There are three types of EUROCAT membership: full, associate, or affiliate. Full member registries send individual records of all congenital anomalies covered by their region. Associate members transmit aggregate case counts for each EUROCAT anomaly subgroup by year and by type of birth. This article describes the organization and activities of each of the current 29 full member and 6 associate member registries of EUROCAT. METHODS: Each registry description provides information on the history and funding of the registry, population coverage including any changes in coverage over time, sources for ascertaining cases of congenital anomalies, and upper age limit for registering cases of congenital anomalies. It also details the legal requirements relating to termination of pregnancy for fetal anomalies, the definition of stillbirths and fetal deaths, and the prenatal screening policy within the registry. Information on availability of exposure information and denominators is provided. The registry description describes how each registry conforms to the laws and guidelines regarding ethics, consent, and confidentiality issues within their own jurisdiction. Finally, information on electronic and web-based data capture, recent registry activities, and publications relating to congenital anomalies, along with the contact details of the registry leader, are provided. CONCLUSIONS: The registry description gives a detailed account of the organizational and operational aspects of each registry and is an invaluable resource that aids interpretation and evaluation of registry prevalence data. Birth Defects Research (Part A) 91: S51-S100, 2011. (C) 2011 Wiley-Liss, Inc.
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| 4. |
- Morgan, Andrei S., et al.
(författare)
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Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France
- 2022
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 111:1, s. 59-75
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). Methods Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. Results Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. Conclusion Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.
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| 5. |
- Tomaz, Simone Annabella, et al.
(författare)
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Physical activity in early childhood education and care settings in a low-income, rural South African community : an observational study
- 2019
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Ingår i: Rural and remote health. - : James Cook University. - 1445-6354. ; 19:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Research has not been conducted on physical activity in early child education and care (ECEC) settings in low- income, rural communities in South Africa. This study aimed to describe the physical activity environment of these settings and identify child and contextual factors associated with physical activity in these settings. By understanding physical activity in this environment, it will be possible to identify context-specific opportunities, including with teachers, to overcome potential challenges and maximise physical activity in a low- and middle- income country setting. Methods: The study was conducted in rural Bushbuckridge, Mpumalanga in 2014. Preschool-aged children (n=55) were recruited from five ECEC settings, including three preschools and two primary schools, where preschool-aged children are in their reception year, grade R. Preschool environment characteristics were assessed using an observational tool adapted from existing tools. Children's physical activity was assessed using the Observational System for Recording Physical Activity in Children- Preschool Version. Differences between preschool and grade R settings were assessed using chi(2) analyses, and multinomial logistic regression analysis was used to determine factors associated with physical activity in the ECEC settings. Results: The physical activity environment differed between preschool and grade R ECEC settings in terms of space (preschoolp<0.001) and fixed equipment (preschool>grade R, p<0.001). On average, children spent 28.7% of their day in the ECEC settings engaged in physical activity, of which 22.3% was moderate- to vigorous-intensity physical activity (MVPA). Children spent the greatest proportion of the day in sedentary activities (69.9%) and this differed significantly between preschool (63.2%) and grade R children (81.3%, p< 0.001). Preschool children were significantly more active than grade R children, and spent greater proportions of time in light-intensity physical activity (8.6% v 2.7%, p<0.001) and MVPA (25.4% v 15.3%, p<0.001). Irrespective of ECEC setting, children were significantly more likely to participate in MVPA if they were outdoors (p=0.001), and significantly less likely to do MVPA if they were overweight/obese (p=0.006). Conclusion: These findings provide insight into child-level and contextual factors associated with preschool-aged children's physical activity within ECEC settings in a low-income, rural community in South Africa. Particularly, the physical and social features of ECEC settings are important in the promotion of physical activity. Findings from this study suggest that it is necessary to upskill and encourage teachers in ECEC settings to maximise opportunities for physical activity in rural low-income communities in South Africa.
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