The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant?

Hum Mutat. 2000 Apr;15(4):385-6. doi: 10.1002/(SICI)1098-1004(200004)15:4<385::AID-HUMU22>3.0.CO;2-A.

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of serositis. To date more then 18 mutations responsible for the disease were identified in the MEFV gene, one such a mutation is E148Q in exon 2 of the gene. While screening FMF patients for mutations in the MEFV gene, we have identified 2 individuals parents of 2 unrelated FMF patients, who were homozygous for E148Q mutation. Upon clinical examination they were absolutely disease free and therefore raised the possibility that this mutation is a benign polymorphism rather than a mutation causing disease. To further investigate the role of the E148Q in FMF we analyzed 25 parents of FMF patients and a control group of 70 individuals, Jews of Moroccan extraction to match for ethnicity of the patients. The rate of E148Q in the control group was 6.4%, being 7.8% among the patient group. Among the parents group (obligatory carriers), in addition to the 2 parents that were homozygous E148Q, in 2 families one of the parents was heterozygote for E148Q but transmitted the other allele (apparently with unknown FMF mutation) to the affected child. Two healthy sibs of one of the E148Q homozygous were also homozygous E148Q. These observations are not in accordance to the notion that E148Q is a mutation causing disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Amino Acid Substitution / genetics*
  • Child
  • Cytoskeletal Proteins
  • Familial Mediterranean Fever / genetics*
  • Female
  • Genetic Variation / genetics*
  • Glutamic Acid / genetics
  • Glutamine / genetics
  • Humans
  • Jews / genetics
  • Male
  • Middle Aged
  • Morocco
  • Mutation / genetics*
  • Pedigree
  • Proteins / genetics*
  • Pyrin

Substances

  • Cytoskeletal Proteins
  • MEFV protein, human
  • Proteins
  • Pyrin
  • Glutamine
  • Glutamic Acid