E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever.
BACKGROUND
Familial Mediterranean fever (FMF) is one of the periodic fever syndromes. It is common among Turks, Jews, Arabs, and Armenians. Several mutations in the MEFV gene, including E148Q, have been identified as causing this disease. It has been suggested that the E148Q mutation is the mildest mutation and some reports have questioned its disease association.


OBJECTIVE
To evaluate the phenotypic features of the patients with E148Q mutation.


METHODS
26 patients homozygous for E148Q, 10 compound heterozygous for E148Q, and eight complex cases were assessed.


RESULTS
Although four of the 26 patients with E148Q/E148Q were asymptomatic at the time of evaluation, abdominal pain was seen in 77% of the patients, fever in 66%, arthralgia in 50%, arthritis in 15.4%, and vomiting in 23.8%. Compound heterozygotes and complex cases had a higher frequency of abdominal pain, fever, arthralgia, arthritis, myalgia, and chest pain than subjects who were homozygous for E148Q, but none of these symptoms reached statistical significance. None of our patients had amyloidosis but two with E148Q/E148Q had a family history of amyloidosis and one had rapidly progressive glomerulonephritis secondary to vasculitis, which progressed to chronic renal failure.


CONCLUSIONS
Patients homozygous for E148Q have a heterogeneous clinical presentation. Most are symptomatic and colchicine treatment is required in these patients.
Hacettepe University Faculty of Medicine, Department of Paediatric Nephrology and Rheumatology, 06100 Ankara, Turkey. rtopalog@.hacettepe.edu.tr
R
R
Topaloglu
F
F
Ozaltin
E
E
Yilmaz
S
S
Ozen
B
B
Balci
N
N
Besbas
A
A
Bakkaloglu
D015746:Abdominal Pain / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005334:Fever / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007592:Joint Diseases / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin