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

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

doi:10.1186/s13023-017-0720-3

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	167
Journal	Orphanet Journal of Rare Diseases
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13023-017-0720-3
Publication status	Published - 2017

Keywords

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

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Papa, R., Doglio, M., Lachmann, H. J., Ozen, S., Frenkel, J., Simon, A., Neven, B., Kuemmerle-Deschner, J. B., Ozgodan, H., Caorsi, R., Federici, S., Finetti, M., Trachana, M., Brunner, J., Bezrodnik, L., Pinedo Gago, M. C., Maggio, M. C., Tsitsami, E., Al Suwairi, W. (2017). A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry. Orphanet Journal of Rare Diseases, 12(1), Article 167. https://doi.org/10.1186/s13023-017-0720-3

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

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",

author = "Riccardo Papa and Matteo Doglio and Lachmann, {Helen J.} and Seza Ozen and Joost Frenkel and Anna Simon and B{\'e}n{\'e}dicte Neven and Kuemmerle-Deschner, {Jasmin B.} and Huri Ozgodan and Roberta Caorsi and Silvia Federici and Martina Finetti and Maria Trachana and Jurgen Brunner and Liliana Bezrodnik and {Pinedo Gago}, {Mari Carmen} and Maggio, {Maria Cristina} and Elena Tsitsami and {Al Suwairi}, Wafaa and Graciela Espada and Anna Shcherbina and Guzide Aksu and Nicolino Ruperto and Alberto Martini and Isabella Ceccherini and Marco Gattorno",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

doi = "10.1186/s13023-017-0720-3",

language = "English",

volume = "12",

journal = "Orphanet Journal of Rare Diseases",

issn = "1750-1172",

publisher = "BioMed Central",

number = "1",

}

Papa, R, Doglio, M, Lachmann, HJ, Ozen, S, Frenkel, J, Simon, A, Neven, B, Kuemmerle-Deschner, JB, Ozgodan, H, Caorsi, R, Federici, S, Finetti, M, Trachana, M, Brunner, J, Bezrodnik, L, Pinedo Gago, MC, Maggio, MC, Tsitsami, E, Al Suwairi, W, Espada, G, Shcherbina, A, Aksu, G, Ruperto, N, Martini, A, Ceccherini, I, Gattorno, M 2017, 'A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry', Orphanet Journal of Rare Diseases, vol. 12, no. 1, 167. https://doi.org/10.1186/s13023-017-0720-3

TY - JOUR

T1 - A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry

AU - Papa, Riccardo

AU - Doglio, Matteo

AU - Lachmann, Helen J.

AU - Ozen, Seza

AU - Frenkel, Joost

AU - Simon, Anna

AU - Neven, Bénédicte

AU - Kuemmerle-Deschner, Jasmin B.

AU - Ozgodan, Huri

AU - Caorsi, Roberta

AU - Federici, Silvia

AU - Finetti, Martina

AU - Trachana, Maria

AU - Brunner, Jurgen

AU - Bezrodnik, Liliana

AU - Pinedo Gago, Mari Carmen

AU - Maggio, Maria Cristina

AU - Tsitsami, Elena

AU - Al Suwairi, Wafaa

AU - Espada, Graciela

AU - Shcherbina, Anna

AU - Aksu, Guzide

AU - Ruperto, Nicolino

AU - Martini, Alberto

AU - Ceccherini, Isabella

AU - Gattorno, Marco

PY - 2017

Y1 - 2017

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.

AB - 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.

KW - Caps

KW - Eurofever

KW - FMF

KW - Genotype-phenotype associations

KW - Hereditary recurrent fevers

KW - Infevers

KW - MKD

KW - Traps

UR - http://www.scopus.com/inward/record.url?scp=85031757744&partnerID=8YFLogxK

U2 - 10.1186/s13023-017-0720-3

DO - 10.1186/s13023-017-0720-3

M3 - Article

C2 - 29047407

SN - 1750-1172

VL - 12

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

IS - 1

M1 - 167

ER -

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

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