ABSTRACT
Background: Genetic generalized epilepsies (GGE) including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and GGE with tonic-clonic seizures alone (GGE-TCS), are common types of epilepsy mostly determined by a polygenic mode of inheritance. Recent studies showed that susceptibility genes for GGE are numerous, and their variants rare, challenging their identification. In this study, we aimed to assess GGE genetic etiology in a Sudanese population. Methods: We performed whole-exome sequencing (WES) on DNA of 40 patients from 20 Sudanese families with GGE searching for candidate susceptibility variants, which were prioritized by CADD software and functional features of the corresponding gene. We assessed their segregation in 138 individuals and performed genotype-phenotype correlations. Results: In a family including three sibs with GGE-TCS, we identified a rare missense variant in ADGRV1 encoding an adhesion G protein-coupled receptor V1, which was already involved in the autosomal recessive Usher type C syndrome. In addition, five other ADGRV1 rare missense variants were identified in four additional families and absent from 119 Sudanese controls. In one of these families, an ADGRV1 variant was found at a homozygous state, in a female more severely affected than her heterozygous brother, suggesting a gene dosage effect. In the five families, GGE phenotype was statistically associated with ADGRV1 variants (0R = 0.9 103). Conclusion: This study highly supports, for the first time, the involvement of ADGRV1 missense variants in familial GGE and that ADGRV1 is a susceptibility gene for CAE/JAE and GGE-TCS phenotypes.
ABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is autoimmune inflammatory disease that attacks the synovium of the joints. Both TNFa and interleukin-1 play crucial roles in the pathogenesis of RA. Gum Arabic (GA) is gummy exudates from Acacia senegal tree. Gum Arabic fermentation by colonic bacteria increases serum butyrate concentrations, so it is considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through its derivative butyrate. To the best of our knowledge, this is the first study conducted to investigate GA intake on inflammatory markers among RA patients. PATIENTS AND METHODS: This is clinical trial phase II in which 40 patients were enrolled aged 18 to 70 years. Patients received 30g/day GA for 12 weeks. TNF α, ESR, and complete blood count were measured and DAS-28 was calculated before and after regular GA consumption. Study was approved by the Ethical committee of National Medicines and Poisons Board. RESULTS: This study showed significant decrease in level of serum TNF α (p value 0.05) [95% CI, 0.65 -16.5], ESR (p value 0.011) [95% CI, 2.6 -18.89], and number of swollen and tender joints in RA patients after 12 weeks of GA intake which reflected as significant decrease in disease severity score DAS 28 P.V:0.00 [95% CI, 1.25 -1.99]. On the other hand, GA had trivial change in blood indices. CONCLUSION: Gum Arabic has favorable immune modulator effect on rheumatoid arthritis. It can be utilized in clinical practice as adjuvant therapy. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov Identifier: NCT02804581 Registered at 19 June 2016, prospective registration.
