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G Grateau

Publications and source records attributed to G Grateau.

At least 19 recordsLinked to original sources
PubMed2003

CIAS1 mutation in a patient with overlap between Muckle-Wells and chronic infantile neurological cutaneous and articular syndromes.

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.

Adult↗
PubMed2001

Recurrent subarachnoid hemorrhage associated with a new transthyretin variant (Gly53Glu).

CNS involvement is rare in systemic amyloidoses due to transthyretin (TTR) mutation and manifests as a combination of dementia, seizures, and myelopathy. The authors report two French siblings who experienced recurrent subarachnoid hemorrhages as the main clinical feature. Brain specimens showed that the leptomeningeal vessels walls were thickened by amyloid deposits, and sequencing of the TTR exons showed a heterozygous single base-pair transition from G to A (codon 53), resulting in a glycine for glutamic acid substitution (G53E).

Adult↗
PubMed2001

Genetically determined recurrent fevers.

The usefulness of molecular diagnosis is now well established for genetically determined recurrent fevers. In familial Mediterranean fever, the severity of the disease and the risk of renal amyloidosis are correlated with mutations in MEFV, and the serum amyloid-associated protein (SAA)1 alpha/alpha allele is a modifying factor for amyloidosis. Study of the genes in various species shows that the human mutations represent a reappearance of the ancestral amino acid state and the B30-2 domain, where most human mutations are localized, is absent in the rat and mouse proteins. Since the discovery of the responsible gene, TNF-receptor-associated periodic syndrome seems to be more frequent than previously considered. Among the new mutations described, some are associated with an incomplete penetrance.

Familial Mediterranean Fever↗
PubMed2001

Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.

Amyloidosis↗
PubMed2001

Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is an autosomal recessive inflammatory disorder characterised by recurrent episode of fever associated with lymphadenopathy, abdominal distress, joint involvement and skin lesions. We recently demonstrated that mutations in the mevalonate kinase gene (MVK) are associated with HIDS. Direct DNA sequencing was done to screen the entire coding region of MVK in 25 unrelated patients with HIDS. Mutations were detected in the coding region of the gene including 11 missense mutations, one deletion, the absence of expression of one allele, as well as three novel polymorphisms. Seven of these mutations are novel. The large majority of the patients were compound heterozygotes for two mutations. Of these, V377I (G-->A) is the most common mutation occurring in 20 unrelated patients and was found to be associated with I268T in six patients. Mutations were associated with a decrease of mevalonate kinase (MK) (ATP:mevalonate 5-phosphotransferase, EC 2.7.I.36) enzymatic activity but not as profound as in mevalonic aciduria, a syndrome also caused by a deficient activity of MK. In HIDS the mutations are located all along the protein which is different from mevalonic aciduria where MK mutations are mainly clustered to a same region of the protein. On the basis of this study, we propose that the diagnostic screen of MVK in HIDS should be first directed on V377I and I268T mutations. Three patients are also described to illustrate the genotypic and phenotypic overlap with mevalonic aciduria.

Adult↗
PubMed2001

[Uveal effusion in its pseudotumoral form. A case report].

Uveal effusion exhibits various clinical presentations, some of which may lead to erroneous diagnosis and mimic a choroidal tumor. A 73-year-old female patient displayed a choroidal lesion with a tumoral appearance spontaneously affecting her right eye. Ultrasonography did not establish the diagnosis, leaving doubt for a tumor. In addition to the tumor - like lesion, a moderate inflammation was found in her right eye. The clinical course was favorable and one month after the initial examination, no fundus abnormalities were observed. The delay imposed by the MRI examination contributed to the lack of any active treatment. Apart from cases occurring postoperatively, the diagnosis of uveal effusion may sometimes be difficult to establish. In order to avoid enucleation and even if ultrasonography is helpful in reaching the correct diagnosis, it seems appropriate to wait and regularly follow up the patients when the diagnosis is not certain. The clinical course might be helpful to establish the diagnosis. Our case suggests that in pseudotumoral forms of uveal effusion, we should repeat clinical examination and ultrasonography in order to manage these patients appropriately.

Aged↗
PubMed2000

Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a recessively inherited disorder predisposing to renal amyloidosis and associated with mutations in MEFV, a gene encoding a protein of unknown function. Differences in clinical expression have been attributed to MEFV-allelic heterogeneity, with the M694V/M694V genotype associated with a high prevalence of renal amyloidosis. However, the variable risk for patients with identical MEFV mutations to develop this severe complication, prevented by lifelong administration of colchicine, strongly suggests a role for other genetic and/or environmental factors. To overcome the well-known difficulties in the identification of modifying genetic factors, we investigated a relatively homogeneous population sample consisting of 137 Armenian patients with FMF from 127 independent families living in Armenia. We selected the SAA1, SAA2, and APOE genes-encoding serum amyloid proteins and apolipoprotein E, respectively-as well as the patients' sex, as candidate modifiers for renal amyloidosis. A stepwise logistic-regression analysis showed that the SAA1alpha/alpha genotype was associated with a sevenfold increased risk for renal amyloidosis, compared with other SAA1 genotypes (odds ratio [OR] 6. 9; 95% confidence interval [CI] 2.5-19.0). This association, which was present whatever the MEFV genotype, was extremely marked in patients homozygous for M694V (11/11). The risk for male patients of developing renal amyloidosis was fourfold higher than that for female patients (OR=4.0; 95% CI=1.5-10.8). This association, particularly marked in patients who were not homozygous for M694V (34.0% vs. 11.6%), was independent of SAA1-allelic variations. Polymorphisms in the SAA2 or APOE gene did not appear to influence susceptibility to renal amyloidosis. Overall, these data, which provide new insights into the pathophysiology of FMF, demonstrate that susceptibility to renal amyloidosis in this Mendelian disorder is influenced by at least two MEFV-independent factors of genetic origin-SAA1 and sex-that act independently of each other.

Adolescent↗
PubMed2000

Mutations in the MEFV gene in a large series of patients with a clinical diagnosis of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessively inherited disease affecting patients of the Mediterranean basin. FMF is characterized by recurrent episodes of fever accompanied with topical signs of inflammation. Some patients can develop a renal amyloidosis associated (AA) amyloidosis. The administration of colchicine is an effective preventive treatment of both the attacks and amyloidosis. The FMF gene (MEFV) was cloned and missense mutations were found to be responsible for the disease. We investigated a large series of 303 unselected and unrelated patients of various ethnic backgrounds with a clinical suspicion of FMF to confirm or invalidate the diagnosis of FMF and to determine the spectrum of MEFV mutations. Molecular analysis focused on all the most frequent mutations identified so far, and an exhaustive analysis of exon 10, containing the mutational hotspot, was performed through DNA sequencing. Sixty-two percent of Sephardic, North African Arabs, Armenian and Turkish patients were either homozygous or compound heterozygous for MEFV mutations. In other populations surrounding the Mediterranean Sea such as Greek, Italian, Portuguese, Kurdish and Lebanese populations, mutations were also found. In general, patients without Mediterranean origin had no mutations in the MEFV gene. Two new mis-sense mutations were identified in exon 10 of the MEFV gene: the S675N in an Italian patient and the M680L in a French patient without any known at-risk ethnic ancestry.

Amino Acid Substitution↗
PubMed2000

A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family.

OBJECTIVE: To characterize both phenotypic (clinical features and magnetic resonance imaging [MRI] findings) and genotypic aspects of autosomal-dominant recurrent fever, also known as tumor necrosis factor receptor (TNFR)-associated periodic syndrome (TRAPS), in a French family and to investigate the role of the mutated 55-kd tumor necrosis factor alpha (TNFalpha) receptor (TNFR1) in the pathogenesis of the disease. METHODS: The coding region of TNFR1 was sequenced in 2 individuals with TRAPS (the propositus and her grandfather) and in 3 clinically unaffected relatives. Expression of soluble TNFR1 (sTNFR1) was investigated in 3 of the family members carrying a C30S mutation in TNFR1, and was compared with the levels of soluble TNFR2 (sTNFR2) by enzyme-linked immunosorbent assay. The membrane TNFR1 expression was then compared with membrane TNFR2 levels at the surface of peripheral blood mononuclear cells by flow cytometric analysis. The clinical heterogeneity in this French family was investigated by searching polymorphic variants in the TNFalpha promoter by DNA sequencing. RESULTS: Both the disease course and the clinical presentation in the propositus were highly indicative of TRAPS. MRI study of the segmental inflammatory process in the limbs showed abnormal signals in the muscle and subcutaneous tissue without involvement of adjacent joints or fascia. A novel missense mutation, C30S, in the first extracellular N-terminal cysteine-rich domain (CRD1) of TNFR1 was characterized in the propositus, her affected grandfather, and her clinically unaffected father. Expression of membrane TNFR1 at the surface of monocytes and polymorphonuclear leukocytes, as well as the levels of sTNFR1 in serum when the disease was not active were not modified in the 3 individuals carrying the TNFR1 C30S mutation. In contrast, during attacks, sTNFR1 levels remained abnormally low, as compared with the levels in unrelated patients with active adult-onset systemic Still's disease. The clinical heterogeneity could not be explained by a polymorphic variant in the TNFalpha promoter. CONCLUSION: TRAPS is a distinct clinical and radiologic disease entity that is responsible for recurrent fever and migratory cellulitis-like processes with localized myositis. We have identified a novel TNFR1 mutation, C30S, that is located in the CRD1 domain in a French family affected by the disease. This mutation seems to affect the level of sTNFR1, which did not increase in the propositus during inflammatory attacks.

Adolescent↗
PubMed2000

A new mutation (A546T) of the betaig-h3 gene responsible for a French lattice corneal dystrophy type IIIA.

PURPOSE: To characterize the betaig-h3 gene defect in a French family affected with lattice corneal dystrophy type IIIA (LCDIIIA). METHODS: Histologic examination was performed from corneal buttons of two patients. Genomic DNA was extracted from leukocytes, and exons of the betaig-h3 gene were amplified by polymerase chain reaction to be directly sequenced. RESULTS: Numerous deposits were evident in the stroma and beneath the Bowman membrane, which had all the features of amyloid deposits. Analysis of exon 12 revealed a heterozygous G to A transition on codon 546. CONCLUSION: In contrast to Japanese patients, these French patients affected with LCDIIIA carry a distinct mutation of the betaig-h3 gene (A546T instead of P501T). Therefore, it is unclear whether different mutations could result in the same dystrophy or whether we are dealing with clinical heterogeneity of LCDIIIA.

Adult↗
PubMed2000

[Diagnostic strategy in amyloidosis].

INTRODUCTION: The diagnosis of amyloidosis is a four-step strategy requiring: 1) a high degree of suspicion, as the clinical presentation of the disease is very polymorphous; 2) the biochemical nature of the disease; 3) the evaluation of the disease spread and 4) how it evolves. EXEGESIS: Simple and noninvasive biopsies usually make it possible to diagnose amyloidosis. Available treatments of generalized amyloidosis require an exact characterization of the nature of amyloid deposits, which is based on the clinical context, immunohistochemical analysis of amyloid deposits, and genetic testing. CONCLUSION: Management of amyloidosis should be improved by better characterization of amyloid deposits. This would result in epidemiological data which are currently lacking.

Amyloid↗
PubMed2000

Clinical versus genetic diagnosis of familial Mediterranean fever.

The diagnosis of familial Mediterranean fever (FMF) has until recently been based on clinical signs alone. Discovery of the MEFV gene has enabled a molecular approach to diagnosis, which is already well established for diagnosing typical clinical forms of FMF. We evaluated the utility of this molecular approach in a large series of patients with various clinical presentations and ethnic origins. We looked for mutations in the MEFV gene in 303 unselected consecutive patients with a variable (from high to low) clinical suspicion of FMF. Two mutations were found in 133 patients (44%). In 22 patients (7%), the clinical diagnosis of FMF was unlikely according to the Tel Hashomer clinical criteria. Our results suggest that the spectrum of FMF-associated signs is broader than previously believed. Wider indications for genotyping should lead to more frequent diagnosis of FMF.

Adolescent↗