TY  - JOUR
A1  - Papa, R
A1  - Doglio, M
A1  - Lachmann, HJ
A1  - Ozen, S
A1  - Frenkel, J
A1  - Simon, A
A1  - Neven, B
A1  - Kuemmerle-Deschner, J
A1  - Ozgodan, H
A1  - Caorsi, R
A1  - Federici, S
A1  - Finetti, M
A1  - Trachana, M
A1  - Brunner, J
A1  - Bezrodnik, L
A1  - Pinedo Gago, MC
A1  - Maggio, MC
A1  - Tsitsami, E
A1  - Al Suwairi, W
A1  - Espada, G
A1  - Shcherbina, A
A1  - Aksu, G
A1  - Ruperto, N
A1  - Martini, A
A1  - Ceccherini, I
A1  - Gattorno, M
UR  - https://doi.org/10.1186/s13023-017-0720-3
VL  - 12
N2  - 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.
AV  - public
JF  - Orphanet Journal of Rare Diseases
EP  - 41
ID  - discovery10029314
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Genetics & Heredity
KW  -  Medicine
KW  -  Research & Experimental
KW  -  Research & Experimental Medicine
KW  -  Hereditary recurrent fevers
KW  -  FMF
KW  -  Caps
KW  -  Traps
KW  -  MKD
KW  -  Infevers
KW  -  Eurofever
KW  -  Genotype-phenotype associations
KW  -  FAMILIAL MEDITERRANEAN FEVER
KW  -  PERIODIC FEVERS
KW  -  MUTATIONS
KW  -  GENE
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article?s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
PB  - BIOMED CENTRAL LTD
TI  - A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry
Y1  - 2017/10/18/
SN  - 1750-1172
ER  -