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Biomedical subjects

C Férec

Publications and source records attributed to C Férec.

At least 73 records · Page 4Linked to original sources
PubMed1996

Linkage disequilibrium between the four most common cystic fibrosis mutations and microsatellite haplotypes in the Celtic population of Brittany.

Microsatellite haplotypes were determined for 117 chromosomes carrying the four most frequent mutations in the cystic fibrosis (CF) gene identified in the Breton population of Celtic origin, as well as for 83 normal chromosomes (noncarriers of a CF mutation). Each of the three non-delta F508 mutations was associated with a single haplotype: 1078deIT with 16-31-13, G55ID with 16-7-17, and W846X with 16-32-13. Although these results suggest identity-by-descent for each mutation, recurrent mutations, although unlikely, could not be completely ruled out. The four most frequent haplotypes on normal chromosomes and the three most frequent haplotypes on delta F508 chromosomes are the same as those found in Ireland, Spain, and Italy. This suggests that some haplotypes, associated or not with the delta F508 mutation, were present in an ancestral population from which all four populations descended.

Cystic Fibrosis↗
PubMed1996

The hereditary pancreatitis gene maps to long arm of chromosome 7.

Hereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. Although this disorder has only been recently described, about 100 families have been documented worldwide. The pathophysiology of this disorder is unknown. Here, a large French family of 147 individuals (47 of whom were affected) from a four-generation kindred with HP has been examined and a genome segregation analysis of highly informative microsatellite markers has been performed. Linkage has been found between HP and six chromosome 7q markers. Maximal two point lod scores between HP and D7S 640, D7S 495, D7S 684, D7S 661, D7S 676 and D7S 688 were 4.00 (theta = 0.143), 5.85 (theta = 0.143), 4.91 (theta = 0.156), 8.58 (theta = 0.077), 8.28 (theta = 0.060), 4.40 (theta = 0.169), respectively. Multipoint linkage data combined with recombinant haplotype analysis indicated that the most likely order is: D7S 640-D7S 495-D7S 684-D7S 661-D7S 676-D7S 688, with the HP gene situated in the underlined region. As in all families reported in the literature, the clinical presentation of the disease is identical to the presentation of sporadic cases, one could expect that the knowledge of the HP gene could be a clue to pancreatitis in general. Based on its map position, this is the first step towards the positional cloning of the Hereditary Pancreatitis Gene (HPG).

Chromosome Mapping↗
PubMed1996

Cystic fibrosis and infertility caused by congenital bilateral absence of the vas deferens and related clinical entities.

The condition of congenital bilateral absence of the vas deferens (CBAVD) is, in the majority of patients, related to defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD patients either are compound heterozygotes (carrying different mutations in their two CFTR genes) or carry a mutation in one of their CFTR genes and an intron 8 5T splice variant, associated with low levels of functional CFTR protein, in their second gene. The relationship between cystic fibrosis (CF) and CBAVD requires a proper clinical examination of the patient, a CFTR mutation analysis for himself and his family and genetic counselling. A mutation analysis should also be performed for the wives of CBAVD males because such couples now have the possibility of having their own genetic children but are at increased risk of having children with CF and/or CBAVD. The aetiology of some conditions of CBAVD is not related to CF, especially when CBAVD is associated with urinary tract malformations (up to 20% of cases). In couples with CBAVD not related to CF there is no increased risk of CF children, but it is not known whether they have an increased risk of having sons with CBAVD. In some of the patients with congenital unilateral absence of the vas deferens (CUAVD) the condition is also related to CF, especially in cases where there is an occlusion of the palpable vas. The CFTR gene is probably not involved in the aetiology of Young's syndrome. Follow-up studies of children born to couples where the males have CBAVD, CUAVD or Young's syndrome are mandatory and will help to better define the risk to their offspring of CF and/or of inheriting their paternal infertility condition.

Cystic Fibrosis↗
PubMed1996

Mutations in the cystic fibrosis gene in men with congenital bilateral absence of the vas deferens.

This paper reviews the relationship between mutations in the cystic fibrosis (CF) gene (CFTR mutations) and congenital bilateral absence of the vas deferens (CBAVD). Two CFTR mutations were identified in 14.5% of the 449 man with CBAVD thus far reported in the literature while one CFTR mutation was found in another 48.1%. CBAVD appears to be a heterogeneous genetic condition, many cases being mild forms of cystic fibrosis, others having no relationship with CF. The 5T allele has also been found in 46% of men with CBAVD, but is not associated by the 'classical' picture of cystic fibrosis. The role of the CFTR gene presumably extends beyond a normal development of the vas deferens, possibly playing a role in spermatogenesis. The detection of CFTR mutations in CBAVD had considerable implications in genetic counselling. Couples requesting microsurgical epididymal sperm aspiration/in-vitro fertilization and those in which the man has CF should be offered CFTR mutations screening if CBAVD is the cause of the male infertility.

Alleles↗
PubMed1996

Distribution of CFTR mutations in cystic fibrosis patients of Tunisian origin: identification of two novel mutations.

Cystic fibrosis (CF), the most common lethal genetic disease in the Caucasian population, is caused by mutations in the CF transmembrane conductance regulator gene (CFTR). More than 500 molecular defects have been reported to date. The distribution of these mutations is both heterogeneous and population related. In Mediterranean populations, 20-30% of CF alleles remain unidentified. We have studied a sample of 39 CF patients of Tunisian origin and have used a GC clamp DGGE assay to scan the CFTR gene. Two novel mutations have been found, but we have been unsuccessful in finding any mutation in 40% of these alleles. These results suggest that, in this Mediterranean population, additional mutations may lie elsewhere in the promoter region or in introns not yet analyzed.

Alleles↗
PubMed1995

Complete screening of mutations in the coding sequence of the CFTR gene in a sample of CF patients from Russia: identification of three novel alleles.

To date, a large number of mutations causing the disease, cystic fibrosis, have been reported worldwide. Having analysed the coding sequence of a sample of cystic fibrosis (CF) patients from Russia, we have identified three novel CF mutations. Two of them, 175 del C in exon 1 and 624 del T in exon 5, are frameshift mutations, predicted to result in premature termination of the CFTR transcript. The third mutation is missense and occurs in exon 12 (D572N). The profile of mutations in this sample of Russian CF patients is particular, with two mutations in exon 13 (2143 del T and 2184 ins A), accounting for 12% of the non-delta F508 alleles.

Alleles↗
PubMed1995

Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses.

We have evaluated a two-tier neonatal cystic fibrosis (CF) screening of immunoreactive trypsinogen (IRT) followed by CFTR gene mutation analysis using a systematic scanning of exons 7, 10, and 11, and, if necessary, by direct DNA sequencing. Over an 18-month period we screened 32,300 neonates born in the western part of Britanny. The first tier, involving IRT screening at 3 days of age, utilizes a low elevation of the trypsinogen level (600 ng/ml), which is highly sensitive. The second tier, which corresponds to the exhaustive screening for mutations in three exons of the gene, is highly specific for this population (Britanny). The false positive rate is very low, and no false negatives have been reported to date. This strategy has allowed the identification of five novel alleles (V322A, V317A, 1806 del A, R553G, G544S).

Base Sequence↗
PubMed1995

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

The spectrum of cystic fibrosis (CF) mutations has been determined in many populations of different ethnic and geographic origins. However, in the south of Europe, the commonest mutation, delta F508, accounts for only about 50% of CF chromosomes, while identification of most of the other mutant alleles has not been achieved. In an ongoing effort to identify these alleles, we have scanned the entire coding sequences of the CF gene using a GC clamp denaturing gradient gel electrophoresis assay in a sample of 57 chromosomes from patients of italian origin. We have identified six novel mutations (C276X, H139R, R117L, S42F, A1006E and 3121-2A---> T). Each has only been found once in this sample of CF patients.

Alleles↗
PubMed1995

HLA class II typing and idiopathic IgA nephropathy (IgAN): DQB1*0301, a possible marker of unfavorable outcome.

Previous studies have reported associations between HLA antigens and Idiopathic IgA Nephropathy (IgAN). Nevertheless most of the studies were performed by serology. Thus we decided to perform the HLA class II typing of 58 patients by molecular biology techniques. We report a small increase of DRB1*04. But the main result of our study is the identification of a strong association between HLA DQB1*0301 and IgAN patients with an unfavorable outcome.

Gene Frequency↗
PubMed1995

p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.

AIMS: To investigate the immunohistochemical expression of p53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours. METHODS: Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. RESULTS: Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium. CONCLUSION: This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis.

Adult↗
PubMed1995

Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients.

Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of sterility in men. Although the genetic basis of this condition is still unclear, it has been shown recently that some of these patients carry mutations in their cystic fibrosis transmembrane conductance regulator (CFTR) genes. To extend this observation, we have analyzed the entire coding sequence of the CFTR gene in a cohort of 67 men with CBAVD, who are otherwise healthy. We have identified four novel missense mutations (A800G, G149R, R258G, and E193K). We have shown that 42% of subjects were carriers of one CFTR allele and that 24% are compound heterozygous for CFTR alleles. Thus, we have been unable to identify 76% of these patients as carrying two CFTR mutations. Furthermore, we have described the segregation of CFTR haplotypes in the family of one CBAVD male; in this family are two male siblings, with identical CFTR loci but displaying different phenotypes, one of them being fertile and the other sterile. The data presented in this family, indicating a discordance between the CBAVD phenotype and a marked carrier (delta F508) chromosome, support the involvement of another gene(s), in the etiology of CBAVD.

Alleles↗
PubMed1994

Identification of three novel mutations (457 TAT-->G, D192G, Q685X) in the Slovenian CF patients.

Chromosomes from a cohort of 60 Slovenian families, corresponding to the 121 cystic fibrosis (CF) chromosomes available, were fully scanned for mutations in the coding sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (The 60 families yielded 121 CF alleles because the mother of one patient was also affected). This corresponds to the 27 exons and intron/exon boundaries that have been studied in chromosomes carrying unidentified alleles. As a result of this survey 84% of the alleles are now clearly identified and we describe in this paper three novel mutations (457 TAT-->G, D192G, and Q685X).

Alleles↗
PubMed1994

Retrospective study of the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Guthrie cards from a large cohort of neonatal screening for cystic fibrosis.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a cAMP-activated chloride channel, and in individuals with both alleles of the gene mutated, symptoms of CF disease are manifest. With more than 300 mutations so far described in the gene the profile of mutant alleles in a population is specific to its ethnic origin. For an analysis with an unbiased recruitment of the CF alleles in neonates of similar origin (Normandy, France), we have retrospectively analyzed the Guthrie cards of affected newborns, diagnosed by the immunoreactive trypsinogen (IRT) assay. Analysis of the 27 exons of the CFTR gene using a GC clamp denaturing gradient gel electrophoresis (DGGE) assay has enabled us to identify over 96% of the mutated alleles. Two of these were novel mutations. We would like to propose this strategy as an efficient method of retrospective molecular genetic diagnosis that can be performed wherever Guthrie cards can be obtained. Knowledge of rare alleles could be a prerequisite for CF therapy in the future.

Base Sequence↗
PubMed1994

Identification of six novel mutations in the CFTR gene of patients from Bulgaria by screening the twenty seven exons and exon/intron boundaries using DGGE and direct DNA sequencing.

The CFTR gene, in which more than 300 mutations have been described, displays a spectrum of mutations which varies according to ethnic and geographic origin of patients. In this paper we report an exhaustive study of the 27 exons and exon/intron boundaries of a sample of 35 CF patients from Bulgaria which is situated in the south east of Europe. We have used denaturing gradient gel electrophoresis assay followed by DNA sequencing and we report the identification of six previously undescribed CFTR alleles.

Amino Acid Sequence↗
PubMed1994

The pancreatitis-associated protein (PAP). A new candidate for neonatal screening of cystic fibrosis.

Neonatal screening of cystic fibrosis (CF) is presently based on immunoreactive trypsin (IRT) assay in blood spots, whose low specificity is a matter of concern. Because the pancreatitis-associated protein (PAP) proved to be a better serum marker of pancreatic alteration than exocrine enzymes, it might be an interesting alternative for CF screening. We report here a preliminary evaluation of the PAP test, conducted in retrospect on blood spots from groups of neonates already screened for CF with the IRT. Neonates with elevated IRT were submitted to subsequent analysis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Neonates with normal IRT (n = 990) or high IRT but normal genotype (n = 28) had normal PAP. Elevated PAP was observed in all CF neonates (n = 11). False-positives for the PAP test were found only among neonates with high IRT and heterozygotes for a mutation in the CFTR gene (6 out of 17 cases). That group represents less than 0.2% of newborns. These results therefore suggest that PAP discriminates CF neonates with a significantly better specificity than IRT.

Antigens, Neoplasm↗