Search PubMed⌕ Search

Biomedical subjects

G Grateau

Publications and source records attributed to G Grateau.

At least 55 records · Page 3Linked to original sources
PubMed1999

MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.

Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessary surgery. Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene. To evaluate the diagnostic and prognostic value of MEFV-gene analysis, we investigated 90 Armenian FMF patients from 77 unrelated families that were not selected through genetic-linkage analysis. Eight mutations, one of which (R408Q) is new, were found to account for 93% of the 163 independent FMF alleles, with both FMF alleles identified in 89% of the patients. In several instances, family studies provided molecular evidence for pseudodominant transmission and incomplete penetrance of the disease phenotype. The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively). The demonstration of both the diagnostic and prognostic value of MEFV analysis and particular modes of inheritance should lead to new ways for management of FMF-including genetic counseling and therapeutic decisions in affected families.

Adolescent↗
PubMed1999

Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44.

The Muckle-Wells syndrome (MWS) is a hereditary inflammatory disorder characterized by acute febrile inflammatory episodes comprising abdominal pain, arthritis, and urticaria. Progressive nerve deafness develops subsequently, and, after several years, the disease is complicated by multiorgan AA-type amyloidosis (i.e., amyloidosis derived from the inflammatory serum amyloid-associated protein) (MIM 191900) with renal involvement and end-stage renal failure. The mode of inheritance is autosomal dominant, but some sporadic cases have also been described. No specific laboratory findings have been reported. The genetic basis of MWS is unknown. Using a genomewide search strategy in three families, we identified the locus responsible for MWS, at chromosome 1q44. Our results indicate that the gene is located within a 13.9-cM region between markers D1S2811 and D1S2882, with a maximum two-point LOD score of 4. 66 (recombination fraction.00) at D1S2836 when full penetrance is assumed. Further identification of the specific gene that is responsible for MWS will therefore provide the first biological element for characterizing MWS, other than doing so on the basis of its variable clinical expression.

Abdominal Pain↗
PubMed1999

Hereditary fevers.

Hereditary fevers are a group of rare disorders of the inflammatory response. Clinical features include recurrent attacks of fever and organ-localized inflammation. Minimal clinical variations, a unique biochemical-specific abnormality, and the mode of genetic inheritance distinguish the three main diseases: familial Mediterranean fever, hyperimmunoglobulinemia D and periodic fever syndrome, and autosomal dominant recurrent fever. The complete elucidation of pathogenesis of these intriguing disorders will be provided by the genetic studies currently in progress.

Familial Mediterranean Fever↗
PubMed1998

[Secondary kidney amyloidosis and mucoviscidosis].

BACKGROUND: Due to the improvement in cystic fibrosis management, life expectancy has risen; on the other hand, longer survival has led to new complications, including secondary renal amyloidosis, which has been so far very uncommonly reported. CASE REPORTS: Secondary nephropathic amyloidosis was seen in two 25-year and 22-year-old adults with cystic fibrosis. Both had developed recurrent pulmonary infections due to Pseudomonas aeruginosa over several years. One patient died after 2 years of progressive kidney failure. CONCLUSION: Severe renal insufficiency due to secondary amyloidosis may complicate the course of cystic fibrosis and become the main prognosis factor in adults.

Adolescent↗
PubMed1998

Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF).

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurring attacks of fever and serositis. It affects primarily North African Jews, Armenians, Turks and Arabs, in which a founder effect has been demonstrated. The marenostrin-pyrin-encoding gene has been proposed as a candidate gene for the disease ( MEFV ), on the basis of the identification of putative mutations clustered in exon 10 (M680V, M694I, M694V and V726A), each segregating with one ancestral haplotype. In a search for additional MEFV mutations in 120 apparently non-founder FMF chromosomes, we observed eight novel mutations in exon 2 (E148Q, E167D and T267I), exon 5 (F479L) and exon 10 (I692del K695R, A744S and R761H). Except for E148Q and K695R, all mutations were found in a single chromosome. Mutation E148Q was found in all ethnic groups studied and in association with a novel ancestral haplotype in non-Ashkenazi Jews (S2). Altogether, these new findings definitively establish the marenostrin/pyrin-encoding gene as the MEFV locus.

Africa, Northern↗
PubMed1998

Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family.

A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct DNA sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in Europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.

Adult↗
PubMed1998

A novel variant of transthyretin (Glu42Asp) associated with sporadic late-onset cardiac amyloidosis.

A sixty-three year old French man presented with isolated late-onset amyloid cardiomyopathy proven by endomyocardial biopsy. There was no known family history of amyloidosis. Immunohistochemistry of cardiac deposits suggested that amyloi fibrils were derived from transthyretin. DNA sequencing revealed a point mutation in exon 2 of the transthyretin gene responsible for a novel amyloidogenic variant Asp42.

Age of Onset↗
PubMed1997

Renal amyloidosis with a frame shift mutation in fibrinogen aalpha-chain gene producing a novel amyloid protein.

A French kindred with autosomal dominant hereditary renal amyloidosis was found to have a novel mutation in the fibrinogen Aalpha-chain gene. In this kindred, renal disease appeared early in life and led to terminal renal failure at an early age. Renal transplantation resulted in rapid destruction of the allograft by amyloid deposition within 2 years. Amyloid fibril protein isolated from a transplanted kidney was found to contain a novel, hybrid peptide of 49 residues whose N-terminal 23 amino acids were identical to residues 499 to 521 of normal fibrinogen Aalpha-chain. The remainder of the peptide (26 residues) represented a completely new sequence for mammalian proteins. DNA sequencing documented that the new sequence was the result of a single nucleotide deletion at position 4897 of the fibrinogen Aalpha-chain gene that gives a frame-shift at codon 522 and premature termination at codon 548. The contributions toward fibrillogenesis of the two portions of the amyloid fibril protein, ie, N-terminal fibrinogen sequence and C-terminal novel sequence, are presently unknown. However, the early onset and rapid reoccurrence of amyloid in renal transplants is unlike the clinical course with other amyloid proteins having single amino acid substitutions that give hereditary renal amyloidosis. Liver transplantation to stop synthesis of this abnormal hepatic derived protein should be considered early in the course of the disease.

Adult↗
PubMed1997

[Hereditary amyloidosis].

Clinical aspects of hereditary amyloidoses are very diverse, and they pose many diagnostic problems to the physician. Biochemical and genetic aspects are also various. Several proteins are implicated in these hereditary diseases: transthyretin, apolipoprotein A1, gelsolin, fibrinogen alpha chain and lysozyme. Studies on structural changes induced by the mutations in these proteins should bring new data relevant to our understanding of the amyloidogenic process. Familial mediterranean fever is a hereditary disease of the inflammatory reaction which is associated with AA amyloidosis.

Amyloidosis↗
PubMed1997

Sphenoid sinus localization of multiple myeloma revealing evolution from benign gammopathy.

BACKGROUND: Plasma-cell neoplasms of the head and neck include extramedullary plasmacytoma and solitary plasmocytoma of bone or may represent a local manifestation of multiple myeloma. Involvement of sphenoid sinus has been rarely reported in multiple myeloma. METHODS: We present the case of a 77-year-old man with a 3-year-history of benign monoclonal IgG-lambda gammopathy who developed left sixth-nerve palsy and malaise. RESULTS: Computed tomography scan and magnetic resonance imaging scan disclosed a large soft-tissue mass of the sphenoid sinus with bone destruction. Sphenoid sinus biopsy revealed an IgG monoclonal plasma cell neoplasm. Diagnosis of multiple myeloma stage IA was then established. CONCLUSIONS: Diagnosis of plasma-cell neoplasm should be considered in sphenoid sinus tumors and depends upon histologic examination. This case enlightens the relationships between monoclonal benign gammopathy and plasma-cell neoplasms of the head and neck which constitute a continuum of B-cell lymphoproliferative disorders.

Aged↗
PubMed1997

Haemophagocytic syndrome in patients infected with the human immunodeficiency virus: nine cases and a review.

We report nine cases of haemophagocytic syndrome (HS) in patients with human immunodeficiency virus infection, and review the 17 cases described to date in the literature. In 21 of 26 cases, HS developed during an advanced stage of immunodeficiency. Clinical and haematological signs are not specific in this setting, and the diagnosis relies on histological features, mainly bone marrow examination. An opportunistic infection was associated in three cases and a lymphoid malignancy in two of our nine cases. The role of the human immunodeficiency virus in the occurrence of the HS remains to be defined. The overall prognosis is poor as six of our nine patients died within 12 months of presentation.

Adult↗