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Rapid Generation of Amyloid from Native Proteins In vitro
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Rapid Generation of Amyloid from Native Proteins In vitro

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Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent

Catherine Dodé1, Bouke P C Hazenberg, Christophe Pêcheux

  • 1Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|July 10, 2002
PubMed
Abstract

Insights

Familial Mediterranean fever (FMF) and TRAPS are key causes of AA amyloidosis in specific ethnic groups. Genetic testing for MEFV and TNFRSF1A mutations is crucial for managing AA amyloidosis linked to inherited recurrent fevers.

Area of Science:

  • Genetics
  • Internal Medicine
  • Rheumatology

Background:

  • Familial Mediterranean fever (FMF) and tumor necrosis factor receptor superfamily 1A (TNFRSF1A) receptor-associated periodic syndrome (TRAPS) are hereditary fevers causing recurrent inflammation and AA type renal amyloidosis.
  • Genetic mutations in MEFV and TNFRSF1A genes are identified causes for FMF and TRAPS, respectively.

Purpose of the Study:

  • To characterize the genotypes of FMF and TRAPS in 38 unrelated patients with AA amyloidosis and recurrent inflammatory attacks.
  • To investigate the genetic basis of AA amyloidosis in patients with recurrent inflammatory episodes.

Main Methods:

  • Genomic DNA was extracted from 38 patients with AA amyloidosis and recurrent inflammatory attacks.
  • Polymerase chain reaction (PCR) was used to amplify MEFV and TNFRSF1A genes, followed by direct sequencing to identify mutations.

Main Results:

  • Mutations in MEFV or TNFRSF1A genes were identified in 27 out of 38 patients (71%).
  • MEFV mutations were prevalent in Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb, with M694V/M694V being the most common genotype.
  • TNFRSF1A mutations were found in three Caucasian patients.

Conclusions:

  • Familial Mediterranean fever (FMF) is the primary cause of AA amyloidosis in Sephardic Jews and Turks.
  • MEFV and TNFRSF1A mutations were identified in a subset of Arab patients from the Maghreb, suggesting other genetic factors may be involved.
  • The study identified families with AA amyloidosis lacking MEFV or TNFRSF1A mutations, indicating the existence of other genetic causes. Genetic characterization is vital for managing AA amyloidosis associated with inherited recurrent fevers.

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