Background The most prevalent autoinflammatory syndromes (AIS) with an identified genetic defect are: Familial Mediterranean Fever (FMF); Tumoral necrosis fator (TNF) Receptor Associated Periodic Syndrome (TRAPS); Pediatric Granulomatous Arthritis (PGA); Cryopyrin Associated Periodic Syndromes (CAPS); and Mevalonate Kinase Deficiency (MKD) 1-3.
Objectives The objective of this Brazilian multicenter study was to determine the prevalence of identifiable genetic defects in patients with a clinical suspicion of AIS from the five regions of the country.
Methods A cross-sectional multicenter study was performed and included 102 patients from 22 Pediatric Rheumatology centers. All patients had a clinical diagnosis of one of the following disorders: CAPS, TRAPS, FMF, MKD and PGA. One of the five AIS-related genes (CIAS1, TNFRSF1A, MEFV, MVK and NOD2) was evaluated in each patient by direct DNA sequencing, based on the most probable clinical suspect. The DNA fragments were directly sequenced and all mutations detected were confirmed in a second PCR product amplification followed by sequencing.
Results The clinical diagnoses of the 102 patients were: CAPS in 28 patients, TRAPS in 31, FMF in 17, MKD in 17 and PGA in 9. Of the 102 patients, 28 (27%) had a confirmed genetic diagnosis by evaluation of only one gene per patient: 6/28 (21%) CAPS patients, 7/31 (23%) TRAPS, 3/17 (18%) FMF, 4/17 (24%) MKD and 8/9 (89%) PGA. Seven (37%) of the different 19 mutations identified were novel, such as T433I and K173E (CIAS1), G87S and D122H (TNFRSF1A), A21V (MVK), and D512H and Y563H (NOD2). One TRAPS patient was homozygous for the G87S mutation.
Conclusions We have found that approximately one third of the Brazilian patients with a clinical suspicion of AIS have a confirmed genetic diagnosis.
Jesus AA, Oliveira JB, Hilario MO et al. Pediatric hereditary autoinflammatory syndromes. J Pediatr (Rio J) 2010;86:353-66.
Glaser RL, Goldbach-Mansky R. The spectrum of monogenic autoinflammatory syndromes: understanding disease mechanisms and use of targeted therapies. Curr Allergy Asthma Rep 2008;8:288-98.
Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27:621-68.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.