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C Férec

Publications and source records attributed to C Férec.

86 records · Page 5Linked to original sources
PubMed1994

[Cystic fibrosis gene mutations in the West of France: clinical application].

The cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the cystic fibrosis phenotype when both alleles are mutated, was cloned and sequenced in 1989. Since then, more than 400 mutations have been reported in the gene, although most of these are rare. We have systematically analysed the entire coding sequence of the CFTR gene in a cohort of patients originating from the West of France (Caen, Brest and Nantes). More than 450 CF children, 914 chromosomes in all, have been exhaustively studied in the three centers. We have been able to characterize more than 90% of the mutations, respectively 93.5%, 99% and 95.8%. Despite the large diversity in the CFTR mutations occurring in CF patients from this area, these results can help to improve genetic counselling, prenatal diagnosis as well as our understanding of the molecular basis of the pathophysiology of cystic fibrosis.

Child↗
PubMed1994

[Linkage between juvenile glaucoma and chromosome 1q in 2 French families].

Primary open-angle glaucoma is a major cause of irreversible blindness in Western countries for which there is presently no curative treatment. Linkage of hereditary juvenile glaucoma with chromosome 1q21-q23 was recently described in 2 American families. Here we have studied two large French pedigrees with a similar form of familial autosomal dominant juvenile-onset glaucoma. Linkage of glaucoma with chromosome 1 was confirmed in these 2 families. Maximal lod-score of 7.60 was reached at the D1S212 marker for a recombination fraction of 4.4%. The typing of this marker should facilitate the screening of glaucoma families and the identification of individuals at risk for the disease. It will also provide a reference to evaluate the genetic heterogeneity of glaucoma.

Adolescent↗
PubMed1993

Screening for cystic fibrosis in dried blood spots of newborns.

We propose a newborn cystic fibrosis (CF) screening test based on the analysis of dried blood spot DNA by a strategy involving simple or multiplex denaturing gradient gel electrophoresis (DGGE) of PCR products of CFTR gene fragments, in conjunction with the immunoreactive-trypsin (IRT) assay. From May 1988 to May 1992 we have performed a neonatal screening programme of 42,000 newborns in Brittany. We identified 450 infants with an elevated IRT level. From this cohort, to evaluate the feasibility of measuring IRT in conjunction with mutation analysis in Guthrie cards, a pilot study was initially conducted on 200 individuals with normal IRT and 150 with raised IRT levels. Furthermore, a retrospective study was performed on 189 IRT positive cards, involving mutation scanning of exons 10 and 11 of the CFTR gene, which contains a number of frequent mutations including the deletion delta F508. We show that this approach has several implications for neonatal CF screening especially in decreasing the recall rate and detecting CF carriers.

Algorithms↗
PubMed1993

A novel mutation in exon 3 of the CFTR gene.

We have screened the 27 exons of the cystic fibrosis transmembrane conductance regulator gene in 87 non-delta F508 chromosomes of Breton origin using the combined techniques of denaturing gradient gel electrophoresis and direct sequencing. By this process, we have detected a new missense mutation, G91R, which results in an arginine for glycine at codon 91. Three affected patients with a delta F508/G91R genotype are pancreatic sufficient. Such observations could facilitate a better understanding of the functional importance of different regions of the encoded product and of the pathogenesis of the disease.

Base Sequence↗
PubMed1993

Identification of 12 novel mutations in the CFTR gene.

Over 200 mutations, besides the deletion delta F508, have been identified in the CFTR gene and are known to cause CF. In order to characterize the molecular defects of non delta F508 CF chromosomes of various French origin, we have combined the techniques of denaturing gradient gel electrophoresis (DGGE) and direct sequencing to screen for mutations in the whole coding sequence of the CFTR gene corresponding to the 27 exons and their exon-intron boundaries. This approach enabled us to identify 12 novel mutations which are described here. We have systematically tested a large number of other nucleotide changes distributed in the 27 exons, each of them was clearly detected. These data support the notion that the DGGE conditions we have defined for screening coding sequence of the CFTR gene allows the identification of most of, if not all, the CFTR gene mutations.

Base Sequence↗
PubMed1993

Genotype analysis of adult cystic fibrosis patients.

To assess the relationship between the genotype and phenotype of adult CF patients we have selected from a group of 512 CF patients attending centres in France, all these of greater than 35 years. We have analysed the entire coding sequence of their CFTR genes. The complete genotype was determined in 7 of the 8 patients and clinical data regarding pancreatic, respiratory and reproductive function were carefully evaluated. All these patients are compound heterozygote, seven carrying the delta F508 and one the G542X on one allele. The other allele carried is: (i) a missense mutation located in exons coding for transmembrane region in five patients [R334W (1); I336K (2); R117H (1); H1054D (1)]; (ii) a splice mutation in two patients [2789 + 5G-->A], (iii) an uncharacterised mutations in one patient. These results strongly suggest less severe CF phenotype to be associated with these mutations and strengthen the hypothesis that less severe phenotype are genetically determined.

Adult↗
PubMed1992

Detection of over 98% cystic fibrosis mutations in a Celtic population.

We have conducted a large systematic study of 365 cystic fibrosis (CF) chromosomes in a Celtic population from Brittany, France, in which we have been able to identify more than 98% of the cystic fibrosis gene mutations. We detected 19 different CFTR mutations located in 9 exons. Eleven of these mutations have not been described previously and nine of them are presented in this study. The denaturing gradient gel electrophoresis strategy we have used, can be applied to other populations suggesting that population screening for CF on a large scale might be possible.

Base Sequence↗
PubMed1986

[Prevention of post-transfusional malaria].

The Authors report the results over a four year-period of their protocol for the detection of blood donors at risk of harboring Plasmodium Falciparum and thence transmitting post-transfusional malaria. This protocol is based on donor questioning and antibody detection by an immunofluorescence assay. It has led to exclude from the direct transfusional network 0,41% of the draws, but then 1032 units have been reintegrated in the inventory without provoking any reported incident. A short study of the geographic origins of the infections confirms the World Health Organization (W.H.O.) data and allows to insist on high risk areas and even reveals previously unsuspected ones. As long as there is no available automated method, and, foremost, no direct parasitemia-detecting assay, this low-cost protocol seems satisfying.

Antibodies↗
PubMed1982

[Antiperinuclear factors in psoriasis. Correlation with other serological abnormalities in 90 patients].

Antiperinuclear factors (APF), studied in 90 patients suffering from psoriasis, were found in psoriasis without arthritis, in psoriasis with psoriatic arthritis and in psoriasis with true rheumatoid arthritis (RA): respectively 57, 36 and 43 p. 100. Patients with APF did not differ from patients without APF apart form rheumatoid factors detected by indirect immunofluorescence. They were much more frequent in psoriasis with APF. These results are compared with those of RA. They lead to look for other auto-antibodies in psoriasis.

Adolescent↗
PubMedDate not supplied

Identification of three novel cystic fibrosis mutations in a sample of Italian cystic fibrosis patients.

An analysis of 274 non-delta F508 Italian cystic fibrosis chromosomes was carried out to determine their molecular defect. In a first step, the delta F508 and 59 other mutations were detected by polyacrylamide gel electrophoresis, restriction digestion, and the amplification refractory mutation system (ARMS) technique. The molecular defects of the other chromosomes were screened for by denaturing gradient gel electrophoresis analysis of exons 3, 4, 7, 11, 12, 13, 14a, 17b, 19 and 20. Direct sequencing was carried out if necessary. This approach allowed us to identify 3 novel mutations, namely M348K, D614G and F693L.

Cystic Fibrosis↗
PubMedDate not supplied

Prenatal diagnosis of cystic fibrosis in different European populations: application of denaturing gradient gel electrophoresis.

The cystic fibrosis transmembrane regulator gene, one of the most commonly mutated in the European population, was cloned in 1989 and since then has been extensively analysed in patients of various ethnic backgrounds. We have screened the entire coding sequences of the cystic fibrosis transmembrane regulator gene and identified many mutations and polymorphisms. In this paper we propose a general strategy to improve prenatal diagnosis and genetic counselling of cystic fibrosis (CF). As this approach based on denaturing gradient gel electrophoresis is adaptable to different populations, it greatly increases the sensibility and specificity of CF prenatal diagnosis.

Chorionic Villi Sampling↗
PubMedDate not supplied

[Molecular epidemiology of cystic fibrosis in Tunisia].

Cystic fibrosis is the most frequent autosomal recessive genetic disease in North European population. This pathology seems to not be rare in Tunisia. On another hand, development of molecular biology techniques has largely contributed to implement the study of the different mutations in the CFTR gene where over 1,300 mutations were reported. Herein, we describe the strategy used to detect molecular defects responsible of cystic fibrosis on 390 children (383 families) in Tunisian population. Several techniques were performed for genotype diagnosis: DNA extraction was from peripheral blood. Polymerase chain reaction (PCR) and polyacylamide gel electrophoresis, and reverse dot blot procedures were used to detect known point mutations. Denaturant gradient gel electrophoresis (DGGE) were used in a next step searching for the unknown point mutations that are later identified by automated sequencing on ABIprism 310. This strategy allowed us to detect 17 different mutations located on the different exons of the CFTR gene. The most frequent was the F508del (50.74%) followed by three other mutations (G542X, W1282X and N1303K) known to be common in the Mediterranean area. For mutations (T665S, 2766 del8, F1166C, L1043R) were exclusively found, up to now, in the Tunisian population. Our results permitted to establish cystic fibrosis mutations and their distribution in Tunisia and to implement an appropriate prevention program of these diseases through the genetic council and prenatal diagnosis.

Child↗
PubMedDate not supplied

[Direct diagnosis of predominant mutation delta F508 associated with the mucoviscidosis gene].

The cystic fibrosis locus was mapped on the long arm of the chromosome 7 in 1985. It has recently been cloned and a three base pair deletion has been recognized as the mutation associated with the majority of CF chromosomes (delta F508). CF haplotypes previously defined with tightly associated DNA markers were analysed using PCR (Polymerase Chain Reaction) and allele specific oligonucleotides to determine the presence or absence of this mutation. This mutation was found on 80% of our CF chromosomes and associated predominantly with the B haplotypes. The detection of this mutation is now a major improvement for carrier detection and prenatal diagnosis of the disease.

Adult↗