Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Diet, physical activity and socio-economic disparities of obesity in Lebanese adults: findings from a national study

Background: The prevalence of obesity within countries varies by gender, age, lifestyle and socioeconomic factors. Identification of behavioural factors that are associated with obesity within the country’s context is critical for the development of effective public health programs which aim to prevent and manage obesity. The objective of this study was to assess age and gender differentials in the prevalence of obesity in Lebanon and examine correlates of obesity with a focus on socioeconomic disparities. Methods: Following the WHO STEPwise guidelines, a national survey was conducted in Lebanon in 2008–2009. Households were selected randomly from all Governorates based on stratified cluster sampling method. One adult aged 20 years and over was randomly selected from each household for the interview. Anthropometric measurements and 24 hour recall dietary intake were obtained. The final sample included 1244 men and 1453 women. Descriptive statistics were computed for BMI, waist circumference, and percent body fat. Multivariate logistic regression analysis was carried out to assess the relationship between energy intake and obesity adjusted for relevant co-variables. Results: The prevalence of obesity among Lebanese adults was 26.1%. Gender differences in obesity estimates were observed across age groups and the three obesity classes, with men showing higher prevalence rates at the younger age groups (20–49 years), and women showing higher prevalence rates in older age groups (50 years and above). Obesity showed significant associations with socio-economic status in women; it decreased with higher educational attainment (OR = 0.54, 95% CI: 0.32, 0.91), greater household assets (OR = 0.26; 95% CI: 0.10, 0.72) and lower crowding index (OR = 0.62; 95% CI: 0.39, 0.98), net of the effect of other co-variates. There was a significant positive association between obesity and energy intake in both genders, and a negative association between obesity and physical activity, significantly among women. Conclusion: Lifestyle and socioeconomic determinants of obesity are identified in this Lebanese population. Policy makers and service providers need to tailor public health strategies to tackle obesity accordingly

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

10.1038/s41467-020-14360-7Nature Communications11159