2427
Özçakar, et al: MEFV gene and HSP
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2008. All rights reserved.
MEFV Mutations Modify the Clinical Presentation of
Henoch-Schönlein Purpura
Z.B
.
IRS
.
INÖZÇAKAR,FATOSYALÇINKAYA,N
.
ILGÜNÇAKAR,BANUACAR,ÖZGÜRKASAPÇOPUR,
DEN
.
IZÜGÜTEN,DERYASOY,NAZLIKARA,NERM
.
INUNCU,N
.
ILAR
.
ISOY,andMES
.
IHAEK
.
IM
ABSTRACT. Objective. Toinvestigatetheprevalenceof MEFV genemutationsinTurkishpatientswithHenoch-
Schönleinpurpura(HSP)butwithnosymptomsoffamilialMediterraneanfever(FMF).Inaddition,
weassessedtheclinicalandlaboratorycharacteristicsofHSPpatientswithandwithout MEFV muta-
tions.
Methods.EightypediatricpatientswithHSP(44boysand36girls)wereenrolled.Bloodformuta-
tionanalysiswasobtainedeitheratthetimeofthediagnosisofHSPorduringfollowupvisitsinpre-
viouslydiagnosedpatients.NopatienthadthediagnosisofFMFintheirhistoryandinthefollowup
period.Exon10ofthe MEFV gene was screened, together with p.E148Q mutation analysis.
Results.Twenty-seven(34%)patientswerefoundtobeheterozygousforoneofthescreened MEFV
mutations; p.M694V in 16, p.M680I in 5, p.V726A in 3, and p.E148Q in 3 patients. Patients with
MEFV mutationswereyoungerthanthosewithoutmutationsandtheyhadedemaandarthritismore
frequently. Also, the frequencies of elevated erythrocyte sedimentation rate and C-reactive protein
valueswerefoundtobesignificantlyhigherinpatientswhohad MEFV mutations.
Conclusion. Alterations in the MEFV gene are important susceptibility factors for the development
of HSP and also affect the clinical presentation of it. (First Release Oct 1 2008; J Rheumatol
2008;35:2427–9; doi:10.3899/jrheum.080405)
Key Indexing Terms:
CHILDREN FAMILIALMEDITERRANEAN FEVER
HENOCH-SCHÖNLEIN PURPURA MEFV GENE
From Ankara University School of Medicine, Department of Pediatric
Nephrology; Ministry of Health Diskapı Children’s Hospital, Department
of Pediatric Nephrology; Ministry of Health Ankara Children’s Hospital,
Department of Pediatric Nephrology, Ankara; and Istanbul University
Cerrahpasa Medical Faculty, Department of Pediatric Rheumatology,
Istanbul, Turkey.
Z.B. Özçakar, MD, Associate Professor; F. Yalçınkaya, MD, Professor,
Ankara University School of Medicine, Department of Pediatric
Nephrology; N. Çakar, MD, Associate Professor, Ministry of Health
Diskapı Children’s Hospital, Department of Pediatric Nephrology;
B. Acar, MD, Ministry of Health Ankara Children’s Hospital, Department
of Pediatric Nephrology; Ö. Kasapçopur, MD, Associate Professor,
Istanbul University Cerrahpasa Medical Faculty, Department of Pediatric
Rheumatology; D. Ügüten, MD, Ankara University School of Medicine,
Department of Pediatric Nephrology; D. Soy, MD; N. Kara, MD;
N. Uncu, MD, Ministry of Health Diskapı Children’s Hospital,
Department of Pediatric Nephrology; N. Arisoy, MD, Professor, Istanbul
University Cerrahpasa Medical Faculty, Department of Pediatric
Rheumatology; M. Ekim, MD, Professor, Ankara University School of
Medicine, Department of Pediatric Nephrology.
Address reprint requests to Dr. F. Yalçinkaya, Çinar Sitesi 5.Blok No:62,
Ümitköy 06530 Ankara, Turkey. E-mail: yalcinkaya@tr.net
Accepted for publication July 17, 2008.
Henoch-Schönlein purpura (HSP) is among the most com-
mon vasculitides of childhood. It is an IgA immune com-
plex-mediated small-vessel vasculitis that classically pres-
ents with the triad of nonthrombocytopenic palpable purpu-
ra, colicky abdominal pain, and arthritis. The exact
causative factor is not known; however, both genetic and
environmentalfactorsarethoughttoplayaroleinthedevel-
opmentofvasculitislikeHSP
1
.Increasedfrequencyofboth
HSP and polyarteritis nodosa (PAN) have been reported in
patientswithfamilialMediterraneanfever(FMF)
2,3
.Thirty-
eight percent of patients with PAN
4
and 30% of patients
with various childhood rheumatic diseases
5
were found to
carry MEFV genemutations.Similarly,patientswithHSPin
Israel have been investigated for the presence of MEFV
mutations and 27% of the patients were found to have
MEFV mutations
6
. The purpose of our study was 2-fold;
first, to investigate the prevalence of MEFV gene mutations
in Turkish patients with HSP who had no symptoms of
FMF;andsecond,toassesstheclinicalandlaboratorychar-
acteristics of HSP patients with and without MEFV muta-
tions.
MATERIALS AND METHODS
Eighty pediatric patients who had been followed in 4 centers in Turkey
betweenSeptember2006andJanuary2008wereenrolled.Allpatientsful-
filled the European League Against Rheumatism/Pediatric Rheumatology
European Society endorsed consensus criteria for the diagnosis of HSP
7
.
Patients with established or suspected diagnosis of FMF according to the
Livneh criteria
8
were excluded, including 6 patients with homozygous
mutationsthatwerediagnosedafterHSP.These6patientswereadmittedto
the hospital with the clinical findings of HSP; 5 of them had FMF symp-
tomsbeforetheonsetofHSPandonedevelopedFMFsymptomsduringthe
followup period after HSP diagnosis. All had elevated acute-phase reac-
tants during HSP attack and colchicine was started in all patients. A ques-
tionnairethatincludedtheclinicalcharacteristicsandlaboratoryfeaturesof
the patients was completed by the physicians. Blood for mutation analysis
wasobtainedeitheratthetimeofdiagnosisofHSPorduringfollowupvis-
itsinpreviouslydiagnosedpatients.Writteninformedconsentwasobtained
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