Biomedical subjects

Marc Delpech

Publications and source records attributed to Marc Delpech.

22 records · Page 2Linked to original sources

PubMed2002

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

BACKGROUND: Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. METHODS: Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. RESULTS: Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene. CONCLUSIONS: In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.

Amino Acid Sequence↗

PubMed2002

Transthyretin mutation (TTRGly47Ala) associated with familial amyloid polyneuropathy in a French family.

A French family in which three individuals had familial amyloid polyneuropathy (FAP) was investigated. The proband presented cardiomyopathy with atrial arrhythmia and then developed axonal polyneuropathy, carpal tunnel syndrome, and sclerodactyly. Nucleotide sequencing of exons 2, 3 and 4 of the transthyretin (TTR) gene revealed heterozygosity for a single base change in the second position of codon 47. This G to C transversion predicts replacement of a glycine by an alanine at position 47 in the mature protein. This mutation (G47A) was previously identified in two different families of Italian origin both of which had FAP and cardiomyopathy. Here we report the first identification of this mutation in a non-Italian family.

Adult↗

PubMedDate not supplied

[Amyloidosis: a model of misfolded protein disorder].

Amyloidosis bears many characteristics of orphan diseases. Its diagnosis is difficult and often delayed. The main reasons thereof are its quite various clinical presentation: amyloidosis behaves as a new great masquerader, and the need to get a tissue sample to submit to specific dyes. Although we have been able for a long time to recognize amyloid, its intimate nature has remained quite completely enigmatic until recently. In fact, major advances in this way have appeared only in the last decade and it is now possible to consider the mechanisms of amyloidosis as a multistep phenomenon. Amyloidosis is no more thought only as a << storage disease >> of the extracellular space. This archaic viewpoint has shifted to the emerging paradigm of misfolded protein disorders. Amyloid proteins thus appear as a subgroup of misfolded proteins, where misfolding leads to subsequent aggregation. This aggregation may be a generic property of polypeptide chains possibly linked to their common peptide backbone that does not depend on specific amino acid sequences. And, in fact, many proteins can in vitro form amyloid-like aggregates, while in vivo, only 20 amyloid proteins have been so far identified. Although misfolding and aggregation are quite well studied in vitro, the last step of amyloid deposition, i.e. anchorage to the extracellular matrix, can not be so easily approached. Proteoglycans and serum amyloid P component have nevertheless been identified as key elements involved in extracellular deposition of amyloid proteins. These advances have opened new avenues in the therapeutic of amyloid disorders. Current treatment consists of support or replacement of impaired organ function and measures to reduce the production of amyloidogenic precursor proteins. Potential novel therapeutic strategies include stabilisation of the native fold of precursor proteins with targeted small molecules, reversion of misfolded proteins to their native state with << beta-sheet breakers >>, inhibition of amyloid fibril propagation and enhancement of amyloid clearance either through immunotherapy or by reducing the stability of deposits through depletion of serum amyloid P component, and breaking the anchorage to the extracellular matrix with glycosaminoglycan analogs.

Amyloid↗

PubMedDate not supplied

TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis.

TNFRSF1A-associated periodic syndrome (TRAPS) and Muckle-Wells syndrome (MWS) are two rare autosomal-dominant inherited periodic fever syndromes found in various populations. The genes involved in these syndromes are respectively TNFRSF1A (TNF receptor 1) and CIAS1 (a gene containing both pyrin and NBS domains). Missense mutations found in these genes are probably responsible for an improvement in function. Renal AA amyloidosis can also be observed.

Amyloidosis↗