Guidelines for the genetic diagnosis of hereditary recurrent fevers

Abstract

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing.Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

Treating TRAPS Syndrome with a Previously Undescribed TNF α Gene Receptor Mutation Successfully with Canakinumab

“…Ген TNFRSF1A кодирует один из рецепто-ров фактора некроза опухоли (Tumor necrosis factor, TNF) ␣ -важнейший провоспалительный цитокин, про-дуцируемый моноцитами/макрофагами, лимфоцитами, NK клетками, полиморфноядерными лейкоцитами [6,12]. Гиперпродукция TNF ␣ играет ведущую патогенетическую роль при многих воспалительных заболеваниях, включая ревматические (ревматоидный артрит, группа серонега-тивных спондилоартритов, ювенильный артрит и др.)…”

“…В результате взаимодействия с рецеп-торами запускается серия внутриклеточных процессов передачи сигнала, что приводит либо к активации фак-тора NF-B и экспрессии генов медиаторов воспале-ния (провоспалительных цитокинов), либо к индукции апоптоза [6,9]. Состояние характеризуется приступами лихорадки, болью в животе и локальными миалгиями.…”

“…Согласно данным, объединяющим результаты иссле-дований, сведения из информационной базы по генным мутациям человека (Human Gene Mutation Database, HGMD), причиной развития TRAPS являются патогенные мутации, расположенные в определенных областях гена TNFRSF1A [5,6].…”

Autoinflammatory Diseases & The Periodic Fever Syndromes

“…Analysis of the fluid reveals 200 to 1,000,000 white blood cells/mm 3 , with a predominance of neutrophils, and an elevated total protein concentration.…”

“…North Africans, for example, are most prone to severe, recurrent attacks of arthritis, while Armenians and Ashkenazi Jews are relatively spared 3 . The arthritis is most often monoarticular or oligoarticular, and the joints most often affected are the knee, ankle, hip, and elbow, in order of frequency.…”