A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry

作者：Papa Riccardo^*; Doglio Matteo; Lachmann Helen J; Ozen Seza; Frenkel Joost; Simon Anna; Neven Benedicte; Kuemmerle Deschner Jasmin; Ozgodan Huri; Caorsi Roberta; Federici Silvia; Finetti Martina; Trachana Maria; Brunner Jurgen; Bezrodnik Liliana; Pinedo Gago Mari Carmen; Maggio Maria Cristina; Tsitsami Elena; Al Suwairi Wafaa; Espada Graciela; Shcherbina Anna; Aksu Guzide; Ruperto Nicolino; Martini Alberto; Ceccherini Isabella; Gattorno Marco

来源：Orphanet Journal of Rare Diseases, 2017, 12(1): 167.

DOI：10.1186/s13023-017-0720-3

• Hereditary recurrent fevers
• FMF
• Caps
• Traps
• MKD
• Infevers
• Eurofever
• Genotype-phenotype associations

Background: Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database (http://fmf.igh.cnrs.fr/ISSAID/infevers) is a large international registry collecting variants reported in these genes. However, no genotype-phenotype associations are provided, but only the clinical phenotype of the first patient(s) described for each mutation. The aim of this study is to develop a registry of genotype-phenotype associations observed in patients with HRF, enrolled and validated in the Eurofever registry.
Results: Genotype-phenotype associations observed in all the patients with HRF enrolled in the Eurofever registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and TRAPS), all mutations were individually analyzed. For autosomal recessive diseases (FMF and MKD), homozygous and heterozygous combinations were described. Mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment were also studied. Data observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the Eurofever registry and validated by experts were summarized in Tables. A total of 149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as various combinations of 48 MVK and 28 MEFV variants were available.
Conclusions: We provide a potentially useful tool for physicians dealing with HRF, namely a registry of genotype-phenotype associations for patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites.

• 出版日期2017-10-18