Related Experiment Video

Updated: May 19, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Familial Mediterranean fever: new phenotypes

Alessandra Soriano1, Raffaele Manna

  • 1Periodic Fever Research Centre, National Reference Centre for FMF, Catholic University of the Sacred Heart, Rome, Italy.

Autoimmunity Reviews
|August 11, 2012
PubMed

Insights

Familial Mediterranean fever (FMF) is an inherited autoinflammatory disorder caused by MEFV gene mutations. Understanding its diverse phenotypes and genetic factors is key to comprehending this complex disease.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Familial Mediterranean fever (FMF) is an inherited autosomal recessive autoinflammatory syndrome.
  • It is primarily observed in individuals of Mediterranean descent and is caused by mutations in the Mediterranean Fever (MEFV) gene.
  • FMF represents the most common periodic febrile syndrome within the spectrum of autoinflammatory diseases.

Purpose of the Study:

  • To delineate the distinct clinical phenotypes of FMF.
  • To explore the genetic underpinnings, including MEFV mutations and their inheritance patterns.
  • To investigate the factors contributing to phenotypic variability and incomplete penetrance in FMF.

Main Methods:

  • Clinical classification into three distinct FMF phenotypes.
  • Genetic analysis focusing on MEFV gene mutations (homozygous, compound heterozygous, and heterozygous states).
  • Consideration of modifier genes and environmental factors influencing disease presentation.

Main Results:

  • Phenotype 1: Recurrent inflammatory episodes with serositis (peritonitis, pleuritis, synovitis).
  • Phenotype 2: AA amyloidosis as the initial manifestation in asymptomatic individuals.
  • Phenotype 3: 'Silent' carrier state with MEFV mutations but no disease symptoms.
  • Identification of 'FMF-like' disease in heterozygous carriers, indicating incomplete or mild forms.

Conclusions:

  • FMF presents with diverse clinical phenotypes, ranging from acute inflammation to amyloidosis and asymptomatic carrier states.
  • MEFV gene mutations are central to FMF pathogenesis, with varying clinical outcomes based on genotype.
  • Genetic modifiers and environmental factors significantly influence FMF penetrance and phenotypic expression, highlighting the disease's complexity.

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages08:23

Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages

Published on: May 30, 2019

Related Concept Videos

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
Patterns of Fever01:26

Patterns of Fever

Before understanding the types and patterns of fever, it is essential to know its phases.
Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism