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Orphanet J Rare Dis. 2017 Oct 18;12(1):167. doi: 10.1186/s13023-017-0720-3.

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

Author information

1
EULAR Centre of Excellence in Rheumatology 2008-2018, IRCCS Istituto Giannina Gaslini, Genoa, Italy. papariccardo86@gmail.com.
2
EULAR Centre of Excellence in Rheumatology 2008-2018, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
3
National Amyloidosis Centre, Royal Free Campus, University College Division of Medicine, London, UK.
4
Department of Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey.
5
Division of Pediatrics, University Medical Center, Utrecht, The Netherlands.
6
Department of Internal Medicine, Radboudumc Expertise Centre for Immunodeficiency and Autoinflammation, Radboudumc, Nijmegen, The Netherlands.
7
Centre de reference national pour les Arthrites Juveniles, Unite d'Immunologie, Hematologie et Rhumatologie Pediatrique, Universite Paris-Descartes, IMAGINE Institute, Hopital Necker-Enfants Malades, Paris, France.
8
Rheumatologisches Zentrum/Ambulanzfur Autoimmunerkrankungen, Universitatsklinikum Tubingen, Tubingen, Germany.
9
Ic Hastalıkları ABD, Romatoloji BD, Istanbul Universitesi Cerrahpaşa Tıp Fakültesi, Istanbul, Turkey.
10
Department of Pediatrics I, Aristotle University of Thessaloniki, Thessaloniki, Greece.
11
Department fur Kinder-und Jugendheilkunde, Klinikfur Padiatrie I, Padiatrische Rheumatologie, Medizinische Universität Innsbruck, Innsbruck, Austria.
12
Immunology Unit, Hospital de Ninos Ricardo Gutierrez, Buenos Aires, Argentina.
13
Unidad de Reumatología Pediátrica, Hospital Universitario Cruces, Bilbao, Spain.
14
Dipartimento Universitario, Ospedale dei Bambini, Palermo, Italy.
15
Pediatric Rheumatology Unit, 1st Department of Pediatrics, Children's Hospital Aghia Sophia, University of Athens, Athens, Greece.
16
Department of Pediatrics, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
17
Seccion Reumatologia, Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina.
18
Research Institute for Paediatric Hematology, Moscow, Russia.
19
EgeUniversitesi Tıp Fakultesi, Pediatrik Romatoloji, Izmir, Turkey.
20
Direzione Scientifica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
21
UOC Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Abstract

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.

KEYWORDS:

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

PMID:
29047407
PMCID:
PMC5648458
DOI:
10.1186/s13023-017-0720-3
[Indexed for MEDLINE]
Free PMC Article

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