A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children
Open Access
- 31 May 2008
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 58 (6) , 1823-1832
Abstract
Objective: To identify a set of clinical parameters that can predict the probability of carrying mutations in one of the genes associated with hereditary autoinflammatory syndromes.Methods: A total of 228 consecutive patients with a clinical history of periodic fever were screened for mutations in the MVK, TNFRSF1A, and MEFV genes, and detailed clinical information was collected. A diagnostic score was formulated based on univariate and multivariate analyses in genetically positive and negative patients (training set). The diagnostic score was validated in an independent set of 77 patients (validation set).Results: Young age at onset (odds ratio [OR] 0.94, P = 0.003), positive family history of periodic fever (OR 4.1, P = 0.039), thoracic pain (OR 4.6, P = 0.05), abdominal pain (OR 33.1, P < 0.001), diarrhea (OR 3.3, P = 0.028), and oral aphthosis (OR 0.2, P = 0.007) were found to be independently correlated with a positive genetic test result. These variables were combined in a linear score whose ability to predict a positive result on genetic testing was validated in an independent data set. In this latter set, the diagnostic score revealed high sensitivity (82%) and specificity (72%) for discriminating patients who were genetically positive from those who were negative. In patients with a high probability of having a positive result on genetic testing, a regression tree analysis provided the most reasonable order in which the genes should be screened.Conclusion: The proposed approach in patients with periodic fever will increase the probability of obtaining positive results on genetic testing, with good specificity and sensitivity. Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened.Keywords
This publication has 25 references indexed in Scilit:
- Recent advances in the molecular pathogenesis of hereditary recurrent feversCurrent Opinion in Allergy and Clinical Immunology, 2006
- A decision tree for genetic diagnosis of hereditary periodic fever in unselected patientsAnnals of the Rheumatic Diseases, 2006
- Approach to genetic analysis in the diagnosis of hereditary autoinflammatory syndromesRheumatology, 2005
- MEFV analysis is of particularly weak diagnostic value for recurrent fevers in Western European Caucasian patientsArthritis & Rheumatism, 2005
- Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndromeNature Genetics, 1999
- Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndromeNature Genetics, 1999
- Germline Mutations in the Extracellular Domains of the 55 kDa TNF Receptor, TNFR1, Define a Family of Dominantly Inherited Autoinflammatory SyndromesCell, 1999
- A candidate gene for familial Mediterranean feverNature Genetics, 1997
- Ancient Missense Mutations in a New Member of the RoRet Gene Family Are Likely to Cause Familial Mediterranean FeverCell, 1997
- Syndrome of periodic fever, pharyngitis, and aphthous stomatitisThe Journal of Pediatrics, 1987