Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients.

[familial mediterranean fever]

Familial Mediterranean fever (FMF ) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV ) mutations . In Japan , patients with FMF have been previously reported , including a mild or incomplete form . Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF . We conducted the current study to investigate the correlation of variable clinical presentations and MEFV genotypic distributions in Japanese FMF patients .We analyzed demographic , clinical , and genetic data for 311 FMF patients enrolled in the study . Clinically , we classified FMF into 2 phenotypes : 1 ) the "typical " form of FMF , and 2 ) the "atypical " form of FMF according to the Tel Hashomer criteria . Patients with the typical FMF phenotype had a higher frequency of febrile episodes , a shorter duration of febrile attacks , more frequent thoracic pain , abdominal pain , a family history of FMF , and MEFV exon 10 mutations . Conversely , patients with the atypical FMF phenotype had a lower frequency of fever episodes and more frequent arthritis in atypical distribution , myalgia , and MEFV exon 3 mutations . Multivariate analysis showed that the variable associated with typical FMF presentation was the presence of MEFV exon 10 mutations . Typical FMF phenotype frequencies were decreased in patients carrying 2 or a single low -penetrance mutations compared with those carrying 2 or a single high -penetrance mutations (M 694 I ), with an opposite trend for the atypical FMF phenotype . In addition , patients having more than 2 MEFV mutations had a younger disease onset and a higher prevalence of thoracic pain than those carrying a single or no mutations . Thus , MEFV exon 10 mutations are associated with the more typical FMF phenotype . In contrast , more than half of the Japanese FMF patients without MEFV exon 10 mutations presented with an atypical FMF phenotype , indicating that Japanese FMF patients tend to be divided into 2 phenotypes by a variation of MEFV mutations .

Diseases
Validation

Diseases presenting "pain" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

aniridia

aromatase deficiency

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cutaneous mastocytosis

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

focal myositis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

junctional epidermolysis bullosa

kabuki syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

malignant atrophic papulosis

neuralgic amyotrophy

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

phenylketonuria

pleomorphic liposarcoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

scrub typhus

sneddon syndrome

systemic capillary leak syndrome

thoracic outlet syndrome

trochlear dysplasia

typhoid

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

wolf-hirschhorn syndrome

This symptom has already been validated