Additional file 1 of Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

Additional file 1: Supplementary Figure 1. Flowchart of included cases in this study. Supplementary Figure 2. Variant filtering and pathogenicity evaluation algorithm. Supplementary Figure 3. Pedigree of included cases in this study. Pedigree a-k are cases 1-12, respectively. The proband is shown by an arrow in each pedigree. Circle and squares represent female and male, respectively. People with same color in each pedigree have same clinical manifestations. Supplementary Figure 4. The structure of protein [1] included in this study and the position of mutated amino acid. a) Structure of human nuclear RNA exosome (PDB: 6H25) [2]. EXOS3 is shown by an arrow and the position of Asp132 which is substituted with Ala in case 1 and 2 b) Structure human tRNA Splicing Endonuclease (TSEN) Complex (PDB: 7UXA) [3]. TSEN2 and TSEN54 are shown by arrows c) Structure of human holo SepSecS (PDB: 7L1T) [4] and the position of Cys70 and His425 which are substituted with Arg in case 4 and 5 d) Structure of AMP deaminase 2 (PDB: 8HUB)[5] and the position of Arg 620 which is substituted with Ser in case 8 e) Structure of CLP1(Swiss model: Q92989) [6] and the position of Leu262 which is substituted with Val in case 9 and Arg140 which is substituted with His in case 10 and 11 f) Structure of TBC1D23 N terminal domain (PDB: 6JL7) [7] and the position of Met 153 which is substituted with Thr in case 12

The global epidemiology and health burden of the autism spectrum: findings from the Global Burden of Disease Study 2021

Background: High-quality estimates of the epidemiology of the autism spectrum and the health needs of autistic people are necessary for service planners and resource allocators. Here we present the global prevalence and health burden of autism spectrum disorder from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 following improvements to the epidemiological data and burden estimation methods. Methods: For GBD 2021, a systematic literature review involving searches in PubMed, Embase, PsycINFO, the Global Health Data Exchange, and consultation with experts identified data on the epidemiology of autism spectrum disorder. Eligible data were used to estimate prevalence via a Bayesian meta-regression tool (DisMod-MR 2.1). Modelled prevalence and disability weights were used to estimate health burden in years lived with disability (YLDs) as the measure of non-fatal health burden and disability-adjusted life-years (DALYs) as the measure of overall health burden. Data by ethnicity were not available. People with lived experience of autism were involved in the design, preparation, interpretation, and writing of this Article. Findings: An estimated 61·8 million (95% uncertainty interval 52·1–72·7) individuals (one in every 127 people) were on the autism spectrum globally in 2021. The global age-standardised prevalence was 788·3 (663·8–927·2) per 100 000 people, equivalent to 1064·7 (898·5–1245·7) autistic males per 100 000 males and 508·1 (424·6–604·3) autistic females per 100 000 females. Autism spectrum disorder accounted for 11·5 million (7·8–16·3) DALYs, equivalent to 147·6 (100·2–208·2) DALYs per 100 000 people (age-standardised) globally. At the super-region level, age-standardised DALY rates ranged from 126·5 (86·0–178·0) per 100 000 people in southeast Asia, east Asia, and Oceania to 204·1 (140·7–284·7) per 100 000 people in the high-income super-region. DALYs were evident across the lifespan, emerging for children younger than age 5 years (169·2 [115·0–237·4] DALYs per 100 000 people) and decreasing with age (163·4 [110·6–229·8] DALYs per 100 000 people younger than 20 years and 137·7 [93·9–194·5] DALYs per 100 000 people aged 20 years and older). Autism spectrum disorder was ranked within the top-ten causes of non-fatal health burden for people younger than 20 years. Interpretation: The high prevalence and high rank for non-fatal health burden of autism spectrum disorder in people younger than 20 years underscore the importance of early detection and support to autistic young people and their caregivers globally. Work to improve the precision and global representation of our findings is required, starting with better global coverage of epidemiological data so that geographical variations can be better ascertained. The work presented here can guide future research efforts, and importantly, decisions concerning allocation of health services that better address the needs of all autistic individuals. Funding: Queensland Health and the Bill & Melinda Gates Foundation.</p

Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. Methods: We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6–7·8] deaths; 10·7% [9·8–11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8–171·6] DALYs; 5·6% [5·0–6·1] of all DALYs). In 2021, there were 93·8 million (89·0–99·3) prevalent and 11·9 million (10·7–13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4–67·7), intracerebral haemorrhage constituted 28·8% (28·3–28·8), and subarachnoid haemorrhage constituted 5·8% (5·7–6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4–117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7–38·1]), diet high in sugar-sweetened beverages (23·4% [12·7–35·7]), low physical activity (11·3% [1·8–34·9]), high systolic blood pressure (6·7% [2·5–11·6]), lead exposure (6·5% [4·5–11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5–10·5]). Interpretation: Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden. Funding: Bill & Melinda Gates Foundation