Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1^−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance. The aim of this study is to analyze the associations between Vitamin D receptor (VDR) gene polymorphism, serum 25-hydroxy vitamin D, metabolic and inflammatory biomarkers in Egyptian obese women. The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels. Their age ranged between 25 and 35 years. Inflammatory biomarkers (interleukin-6 and C-reactive protein) and serum 25(OH) D were measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR).Vitamin D receptor (VDR) gene polymorphisms of FokI, ApaI, and TaqI were studied by PCR using the restriction fragment length polymorphism (RFLP) technique. Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls. Multivariable-logistic regression showed associations between 25(OH) D deficiency and metabolic components when comparing cases with controls. Moreover, cases carrying polymorphic alleles showed significant lower levels of serum 25(OH) D and higher HOMA-IR, blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency. Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers. Moreover, VDR polymorphisms play important role in immune and inflammation status.

Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

O1 Regulation of genes by telomere length over long distances

Introduction: To assess the prevalence of metabolic risk indicators for the metabolic syndrome (MS) in a sample of obese Egyptian adolescents and to compare anthropometric and biochemical parameters in subjects with one or two parameters of the MS with those who meet MS criteria. Material...