Biomedical subjects
Publications and source records attributed to F Duclos.
We report a case of recurrent transudative pleural effusion. The initial cardiovascular investigations failed to determine its cause. The catheterization showed a "dip-plateau" suggesting a restrictive cardiomyopathy. Endomyocardial biopsy finally proved a cardiac amyloidosis.
The Friedreich's ataxia locus (FRDA) is tightly linked to markers D9S5 and D9S15 located in 9q13-q21. Cumulated maximum lod scores between FRDA and D9S5 and between FRDA and D9S15 are above 36 and 61, respectively, at a recombination fraction of 0, indicating that recombination events needed to orient the search of the gene are very difficult to identify and ascertain. We have established a 1 Megabase PFGE map around D9S5 and D9S15 and isolated a corresponding 530 kb YAC contig. We found that the two markers are 260 kb apart. This result was surprising, since D9S5 and D9S15 were independently isolated, but in agreement with the strong linkage between the two loci (lod score > 35 at a recombination fraction of 0). Seven clusters of rare cutter enzyme sites (CpG islands), which are potential indicators of genes, were identified in the 1 Megabase region by PFGE analysis and YAC mapping. The search for genes around the CpG islands is in progress. To map the Friedreich ataxia locus in the absence of clearly identified recombination events, we chose an alternative approach based on haplotype analysis of patients from small populations with precise geographic and historical origins, such as the Louisiana-Acadians, deported from Nova-Scotia about 150 years ago and who remained isolated for historical and cultural reasons. In this population, a single mutation, associated with a specific haplotype may account for the majority of Friedreich ataxia cases. Haplotypes different from the major haplotype at one or the other extremity can indicate ancient recombinations.(ABSTRACT TRUNCATED AT 250 WORDS)
Friedreich ataxia is a severe neurodegenerative autosomal recessive disorder of unknown biochemical defect. The Friedreich ataxia locus (FRDA) is tightly linked to the centromeric side of the D9S5 locus. We have used 'exon-trapping' to identify two new genes, approximately 100 and 200 kb centromeric to D9S5, respectively. One gene appears ubiquitously expressed while the other is prominently expressed in muscle. The ubiquitous transcript codes for a protein containing a 20 aa repeat reminiscent of simple repeats found in several ribonucleoproteins. Using the single-strand conformation polymorphism (SSCP) procedure, we searched for mutations in affected patients in the coding sequence of the two genes, as well as in a gene that we had previously identified in the same region. Eight polymorphic DNA changes but no causative mutations were found, suggesting that the genes are not candidates for Friedreich ataxia. The discovery of a simple sequence repeat polymorphism in the most centromeric gene allowed the localization within that gene of the breakpoint of a previously described recombination in a Friedreich ataxia family, therefore excluding the two distal genes from the FRDA region. The lack of causative mutations in the three genes and the position of the recombination further delineate the FRDA locus to a 300 kb interval.
The locus for Friedreich ataxia (FRDA), a severe neurodegenerative disease, is tightly linked to markers D9S5 and D9S15, and analysis of rare recombination events has suggested the order cen-FRDA-D9S5-D9S15-qter. We report here the construction of a YAC contig extending 800 kb centromeric to D9S5 and the isolation of five new microsatellite markers from this region. In order to map these markers with respect to the FRDA locus, all within a 1-cM confidence interval, we sought to increase the genetic information of available FRDA families by considering homozygosity by descent and association with founder haplotypes in isolated populations. This approach allowed us to identify one phase-known recombination and one probable historic recombination on haplotypes from Réunion Island patients, both of which place three of the five markers proximal to FRDA. This represents the first identification of close FRDA flanking markers on the centromeric side. The two other markers allowed us to narrow the breakpoint of a previously identified distal recombination that is > 180 kb from D9S5 (26P). Taken together, the results place the FRDA locus in a 450-kb interval, which is small enough for direct search of candidate genes. A detailed rare cutter restriction map and a cosmid contig covering this interval were constructed and should facilitate the search of genes in this region.
Friedreich ataxia (FRDA) is an autosomal recessive degenerative disorder that affects the cerebellum, spinal cord, and peripheral nerves. The FRDA gene was localized in 9q13-q21 within 0.7 centimorgan of the D9S5 and D9S15 loci. One recently reported recombination event and haplotype analysis in a population with a founder effect suggested that the FRDA locus is on the D9S5 side. Using a conserved probe from the D9S5 locus, we have now identified an approximately 7-kilobase (kb) transcript and report cloning of its cDNA. The corresponding gene, X11, extends at least 80 kb in a direction opposite D9S15. The gene is expressed in the brain, including the cerebellum, but is not detectable in several nonneuronal tissues and cell lines. In situ hybridization of adult mouse brain sections showed prominant expression in the granular layer of the cerebellum. Expression was also found in the spinal cord. The cDNA contains an open reading frame encoding a 708-amino acid sequence that shows no significant similarity to other known proteins but contains a unique, 24-residue-long, putative transmembrane segment. On the basis of its genomic localization and its neuronal site of expression, particularly in the cerebellum, this "pioneer" gene represents a candidate for FRDA. Direct evidence of its involvement in FRDA will require a search for causative point mutations in patients.
Linkage studies with DNA polymorphic markers allowed to map the loci of three inherited ataxia and to explore genetic heterogeneity in inherited ataxia in general. The locus of Friedreich ataxia, the most frequent of all recessive ataxias, has been mapped in 9q13-q21. In addition, Friedreich ataxia is an homogeneous genetic entity since all families from all populations tested (mainly European, North-American and from the Mediterranean basin) show linkage with this locus. But the severity of the disease varied in a few families. A form of recessive ataxia associated with a selective and severe serum vitamin E deficiency, which frequently presents clinically like typical Friedreich ataxia, is not linked to 9q13-q21 markers. The autosomal recessive spastic ataxia from Charlevoix-Saguenay (a region of Quebec) is also not linked to these markers. Both entities are therefore distinct genetically from Friedreich ataxia. Among dominant ataxias, the most important group is olivo-ponto-cerebellar ataxia which is heterogeneous and for which any classification is hindered by important intra-familial variability. This group corresponds to at least three distinct loci, two of which have been mapped, one in 6p23-p24, and the other, more recently, on chromosome 12. Prenatal and presymptomatic diagnosis based on linked markers can be made for the three mapped ataxias, but only in families with an affected individual for whom the diagnosis has been ascertained by through clinical investigation or by linkage analysis if the family is large enough (mainly for the dominant diseases). Linked markers are also the first tools for the search of the defective genes by positional cloning.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors report the case of a patient who, during percutaneous transluminal angioplasty of the circumflex artery, developed sudden occlusion of the anterior interventricular artery without stenosis and not touched by the operator. The fact that this occlusion was completely reversible after an intra-coronary injection of nitroglycerin suggests that this was due to spasm. This case suggests the possibility of consequences of angioplasty at a point distant from the dilated site. The authors use this case and a review of the literature to discuss the pathophysiological mechanisms which could be responsible for such consequences.
Friedreich ataxia (FA) is a severe autosomal recessive neurodegenerative disease. The defective gene has been previously assigned to chromosome 9q13-q21 by demonstration of tight linkage to the two independent loci D9S15 and D9S5. Linkage data indicate that FRDA is at less than 1 cM from both markers. Previous physical mapping has shown that probes defining D9S15 (MCT112) and D9S5 (26P) are less than 260 kb apart and are surrounded by at least six CpG clusters within 450 kb, which might indicate the presence of "candidate" genes for FA. We isolated and characterized a 530 kb YAC (yeast artificial chromosome) contig that contains five of the CpG clusters. The YACs were used to search for new polymorphic markers needed to map FRDA precisely with respect to the cloned segment. In particular, we found a (CA)n microsatellite polymorphism, GS4, that detects 13 alleles with a PIC value of 0.83 and allows the definition of haplotypes extending over 310 kb when used in combination with polymorphic markers at D9S5 and D9S15.
Eleven Acadian families with Friedreich ataxia (FA) who were from southwest Louisiana were studied with a series of polymorphic markers spanning 310 kb in the D9S5-D9S15 region previously shown to be tightly linked to the disease locus. In particular, three very informative microsatellites were tested. Evidence for a strong founder effect was found, since a specific extended haplotype spanning 230 kb from 26P (D9S5) to MCT112 (D9S15) was present on 70% of independent FA chromosomes and only once (6%) on the normal ones. There was no evident correlation between haplotypes and clinical expression. The typing of an additional microsatellite (GS4) located 80 kb from MCT112 created a divergence of the main FA-linked haplotype, generating four minor and one major haplotype. A similar split was observed with GS4 in a patient homozygous for a rare 26P-to-MCT112 haplotype. These results suggest that GS4 is flanking marker for the disease locus, although other interpretations are possible.
The authors report the case of 21-year old female patient with a particular form of Takayasu's disease remarkable for its initial presentation and its cardiac and coronary lesions. The disease began with miscarriage at the 5th months of pregnancy, followed by acute pericarditis with tamponade. Subsequently, lesions of the aortic and mitral valves developed, while the myocardium became involved with left ventricular dilatation and hypokinesia confirmed by echocardiography and cineangiography. Coronary arteriography revealed large coronary aneurysms which are exceptional in this disease. This case prompted the authors to discuss the various cardiac lesions and the relationship of Takayasu's disease with pregnancy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fifteen patients were treated with low-dose (5 u/hour) insulin infusion, including 10 cases of ketoacidosis, 3 cases of hyperglycemia without acidosis in severely affected diabetics, and 2 cases with hyperosmolality. The treatment was successful in all cases. Insulin was infused at a constant rate, during 12 hours as a mean value. Blood glucose fell regularly and no hypoglycemia occured. Serum potassium varied within narrow limits, and no accident related to hypokalemia was observed. The correction of ketoacidosis was delayed, as compared to that of hyperglycemia. The two elderly patients with hyperosmolality recovered quickly and completely. The method of low-dose insulin infusion seems thus effective and easily applicable, at least in an intensive care unit. Our experience prompted us to increase (10 u/h) rather than to decrease the insulin infusion rate, with the aim to obtain a faster correction of ketoacidosis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.