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

被引：51

作者：

Papa, Riccardo ^{[1
]}

Doglio, Matteo ^{[1
]}

Lachmann, Helen J. ^{[2
]}

Ozen, Seza ^{[3
]}

Frenkel, Joost ^{[4
]}

Simon, Anna ^{[5
]}

Neven, Benedicte ^{[6
]}

Kuemmerle-Deschner, Jasmin ^{[7
]}

Ozgodan, Huri ^{[8
]}

Caorsi, Roberta ^{[1
]}

Federici, Silvia ^{[1
]}

Finetti, Martina ^{[1
]}

Trachana, Maria ^{[9
]}

Brunner, Jurgen ^{[10
]}

Bezrodnik, Liliana ^{[11
]}

Pinedo Gago, Mari Carmen ^{[12
]}

Maggio, Maria Cristina ^{[13
]}

Tsitsami, Elena ^{[14
]}

Al Suwairi, Wafaa ^{[15
]}

Espada, Graciela ^{[16
]}

Shcherbina, Anna ^{[17
]}

Aksu, Guzide ^{[18
]}

Ruperto, Nicolino ^{[1
]}

Martini, Alberto ^{[19
]}

Ceccherini, Isabella ^{[20
]}

Gattorno, Marco ^{[1
]}

机构：

[1] IRCCS Ist Giannina Gaslini, EULAR Ctr Excellence Rheumatol 2008 2018, Genoa, Italy

[2] UCL, Div Med, Natl Amyloidosis Ctr, Royal Free Campus, London, England

[3] Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey

[4] Univ Med Ctr, Div Pediat, Utrecht, Netherlands

[5] Radboudumc, Dept Internal Med, Radboudumc Expertise Ctr Immunodeficiency & Autoi, Nijmegen, Netherlands

[6] Univ Paris 05, Ctr Reference Natl Arthrites Juveniles, Unite Immunol Hematol & Rhumatol Pediat, IMAGINE Inst,Hop Necker Enfants Malad, Paris, France

[7] Univ Klinikum Tubingen, Rheumat Zentrum Ambulanz Autoimmunerkrankungen, Tubingen, Germany

[8] Istanbul Univ, Ic Hastaliklari ABD, Romatol BD, Cerrahpasa Tip Fak, Istanbul, Turkey

[9] Aristotle Univ Thessaloniki, Dept Pediat 1, Thessaloniki, Greece

[10] Med Univ Innsbruck, Dept Kinder & Jugendheilkunde, Klin Padiatrie 1, Padiatr Rheumatol, Innsbruck, Austria

[11] Hosp Ninos Dr Ricardo Gutierrez, Immunol Unit, Buenos Aires, DF, Argentina

[12] Hosp Univ Cruces, Unidad Reumatol Pediat, Bilbao, Spain

[13] Osped Bambini Brescia, Dipartimento Univ, Palermo, Italy

[14] Univ Athens, Childrens Hosp Aghia Sophia, Dept Pediat 1, Pediat Rheumatol Unit, Athens, Greece

[15] King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Riyadh, Saudi Arabia

[16] Hosp Ninos Dr Ricardo Gutierrez, Secc Reumatol, Buenos Aires, DF, Argentina

[17] Res Inst Paediat Hematol, Moscow, Russia

[18] EgeUniv, Pediat Romatol, Tip Fak, Izmir, Turkey

[19] IRCCS Ist Giannina Gaslini, Direz Sci, Genoa, Italy

[20] IRCCS Ist Giannina Gaslini, UOC Med Genet, Genoa, Italy

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2017年 / 12卷

关键词：

Hereditary recurrent fevers; FMF; Caps; Traps; MKD; Infevers; Eurofever; Genotype-phenotype associations; FAMILIAL MEDITERRANEAN FEVER; PERIODIC FEVERS; MUTATIONS; GENE;

D O I：

10.1186/s13023-017-0720-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：41

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