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Biomedical subjects

B Simon-Bouy

Publications and source records attributed to B Simon-Bouy.

52 records · Page 3Linked to original sources
PubMed1992

Carrier detection and prenatal diagnosis of cystic fibrosis using an intragenic TA-repeat polymorphism.

We have analysed the segregation of a TA-repeat polymorphism in intron 17b of the cystic fibrosis transmembrane conductance regulator gene responsible for cystic fibrosis (CF) in 23 French CF families non-informative for the delta F508 mutation (i.e. with at least one parent not carrying delta F508) or closely linked DNA markers. At least 13 different alleles ranging from 7 to 45 repeats were observed and the detected heterozygosity was 89%. Of the 23 families studied, 19 were fully informative for prenatal diagnosis or carrier detection, 3 were partially informative and one was not informative. In 6 families, prenatal diagnosis for CF or carrier detection in siblings of CF cases were performed using this polymorphism.

Base Sequence↗
PubMed1992

[Accidental ultrasonographic disclosure of isolated intra-abdominal fetal hyperechogenicity. Apropos of a series of 87 cases].

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyperechogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

Amniotic Fluid↗
PubMed1991

Functional insertion of the SV40 large T oncogene in cystic fibrosis intestinal epithelium. Characterization of CFI-3 cells.

Intestinal epithelial cells were isolated from a fetus with cystic fibrosis (CF) and transfected with a plasmid vector recombined with the ori- mutant of SV40. A population of proliferative cells was then subcloned and designated as CFI-3. These cells had a doubling time of 24 h and were maintained in culture for up to 25 passages. At passage 8, CFI-3 cells did not produce any tumors in nude mice. Northern blot and immunofluorescence studies indicated that the extended lifespan of CFI-3 cells results in genomic insertion of SV40 LT. Intestinal CFI-3 cells are epithelial, according to the expression of the human cytokeratin 18 gene and poorly differentiated by phase-contrast and electron microscopy. Functional membrane receptors activated by vasoactive intestinal peptide (VIP), its natural analogue pituitary adenylate cyclase activating peptide (PACAP-38), and isoproterenol were observed in CFI-3 cells. Restriction fragment length polymorphism analysis of the PstI KM19 site revealed that the cftr locus was identical in the chorionic villi and in CFI-3 cells. The manifestation of CF in this family was not related to the common mutation delta F508, since this fetus was heterozygous for the substitutions S549N and N1303K. Chloride transport, assessed by the 125I efflux, was induced in CFI-3 cells by the calcium inophore ionomycin, but not by the adenylate cyclase activator forskolin, and was inhibited by the chloride channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid. These results were confirmed in patch clamp studies in which the cpt cAMP analogue failed to stimulate membrane currents, while the calcium ionophore ionomycin stimulated inward currents. We conclude that intestinal CFI-3 cells retain the CF phenotype relating to defective regulation of Cl- channels, and therefore constitute a suitable model, 1) for elucidating the function of CFTR protein, 2) developing new therapeutic agents, and 3) correcting the CF defect by gene replacement therapy in vitro.

Antigens, Polyomavirus Transforming↗
PubMed1991

Consequences of prenatal diagnosis of cystic fibrosis on the reproductive attitudes of parents of affected children.

Three hundred and twenty-six French families with a cystic fibrosis-affected child who were referred for prenatal diagnosis were analysed by sibship size: 74.2 per cent of the couples had no further pregnancies to term after the affected child, who was deceased in 34.6 per cent of cases. These couples were followed prospectively after prenatal diagnosis and 77 had two or more consecutive pregnancies with prenatal diagnosis. The aim of these couples was to succeed in constituting a family with two normal children.

Alkaline Phosphatase↗
PubMed1991

Nearly 80% of cystic fibrosis heterozygotes and 64% of couples at risk may be detected through a unique screening of four mutations by ASO reverse dot blot.

A technique allowing the simultaneous screening of the four main CF mutations in the French population (delta F508, delta I507, G542X, S549N) has been developed by means of allele sequence-specific oligonucleotide (ASO) reverse dot blot. Using a strategy proposed by R. K. Saïki et al. (1989, Proc. Natl. Acad. Sci. USA 86: 6230-6234) for HLA-DQA, the seven ASOs for normal and mutant CF alleles were given a homopolymer T tail with terminal deoxyribonucleotidyltransferase and then immobilized on a nylon membrane. T-tail homopolymers were preferentially bound to the nylon, leaving the specific ASO sequences free to hybridize with amplified and radiolabeled exons 10 and 11 of a patient. These exons were simultaneously coamplified by a multiplex PCR and radiolabeled by random priming. ASO reverse dot blot currently appears to be the most efficient, rapid, and economic means of screening the population for CF mutations. This screening can detect nearly 80% of carriers and 64% of couples at risk and could prevent the birth of CF-affected infants in these families.

Alleles↗
PubMed1991

Nine mutations in the cystic fibrosis (CF) gene account for 80% of the CF chromosomes in French patients.

Thirteen mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been screened in a French sample of 185 cystic fibrosis (CF) patients, together with their respective associated RFLP haplotypes at the linked D7S23 locus (XV2C and KM19 markers). The respective frequencies of the mutations showed that 9 of them account for 80% of the CF chromosomes. Implications for prenatal diagnosis and heterozygote detection are defined and discussed. The well-known great excess of RFLP B marker within CF chromosomes is partially explained by two already characterized mutations highly associated with haplotype B: delta F508 and G542X. Similarly, the excess of haplotype D within CF chromosomes is partially explained by the association between delta I507 and this haplotype. These results may suggest the existence of two still untested or uncharacterized mutations, whose frequencies could be near 1%, one which would be associated with haplotype B and a second which would be associated with haplotype D. The possible cause of the specific association between most of the main different CF mutations and the RFLP haplotype B is discussed.

Alleles↗
PubMed1991

[Fortuitous discovery in echography of an isolated fetal intra-abdominal hyperechogenic mass. 87 cases].

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyper-echogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

Amniocentesis↗
PubMed1990

Localization of the gene for amiloride binding protein on chromosome 7 and RFLP analysis in cystic fibrosis families.

The apical sodium channel is essential for sodium reabsorption by the kidney. Its activity is blocked by the diuretic amiloride. Using a human cDNA coding for the amiloride binding protein (ABP), the corresponding structural gene was mapped to human chromosome 7q34-q36 by in situ hybridization. This region flanks the region implicated in cystic fibrosis (7q32). Because an alteration of the amiloride sensitive sodium channel function has been suggested in cystic fibrosis, a possible link between the ABP gene and this disease was analyzed by restriction fragments length polymorphism (RFLP) analyses. From this study, it appears that the gene coding for ABP is not directly modified by mutations causing cystic fibrosis.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Studies of RFLP closely linked to the cystic fibrosis locus throughout Europe lead to new considerations in populations genetics.

The prenatal diagnosis of cystic fibrosis is now routinely performed by using two probes tightly linked to the CF locus (XV2C and KM19). These probes have been shown to exhibit a strong linkage disequilibrium with the CF locus. Our data (103 families) have been pooled with other French data (237 families). They are consistent with the hypothesis of a unique ancestral mutation initially associated with a B (D1E2) restriction fragment length polymorphism (RFLP) haplotype, subsequently reassociated by cross-over with A, C or D haplotypes. Assuming such an hypothesis, the mutation is supposed to be 3000-6000 years old, depending on generation length and the true recombination ratio between the KM19 and CF loci. Up-to-date Spanish, Danish and Greek data are reported together with other previously published population data in order to discuss the geographic origin and age of the mutation in Europe. The action of selection in terms of heterozygote advantage and distorsion of segregation is discussed.

Cystic Fibrosis↗
PubMed1990

Genotyping of the Spanish cystic fibrosis population at the delta F508 mutation site and RFLP linked loci.

Spanish families (n = 75) with at least one affected cystic fibrosis (CF) child were typed for restriction fragment length polymorphisms (RFLPs) by the probes XV2c, KM19, and pMP6d-9. These families were also studied at the 508 mutation site by the polymerase chain reaction method. We have studied the linkage disequilibrium between these markers and the CF mutations, the probable number of independent secondary CFX (non-delta F508) mutations, and the genetic differences between Spain and Western Europe.

Chromosome Deletion↗
PubMed1990

The cystic fibrosis delta F508 mutation in the French population.

French families (n = 129) with at least one cystic fibrosis (CF) affected child and 44 unrelated subjects from the general population were tested for the presence of the delta F508 mutation by the polymerase chain reaction. The delta F508/CF mutation ratio (CF: uncharacterised CF mutations) was tested in the CF families with and without meconium ileus. The association between delta F508 and CF mutations and restriction fragment length polymorphism haplotypes (XV2c and KM19) has been estimated; these data suggest that the CF chromosomes include a panel of independent and probably different mutations.

Cystic Fibrosis↗
PubMed1989

Genetic heterogeneity between two clinical forms of cystic fibrosis evidenced by familial analysis and linked DNA probes.

CF heterogeneity has been evidenced from both clinical and genetic observations. At least two clinical forms of CF are easily distinguishable: CF with meconium ileus and CF without meconium ileus. The results of prenatal diagnosis have shown that the recurrence rates of CF are different in these two clinical forms. Molecular analysis of Restriction Fragment Length Polymorphisms (RFLPs) tightly linked to the cystic fibrosis (CF) gene defined several types of CF and normal chromosomes in a French sample of 64 families with CF. The CF mutation is tightly linked to one XV-2C and KM19 RFLPs haplotype but is differently linked to J3.11 RFLP alleles, depending on whether or not the clinical form of CF is associated with ileus. A distortion of the segregation ratio observed between normal and CF haplotypes in the families with ileus could explain the high recurrence rate of CF in such families.

Alleles↗
PubMed1988

Genetic differences between cystic fibrosis with and without meconium ileus.

41 families with cystic fibrosis, (CF) were tested for restriction fragment length polymorphisms (RFLPs) detected by four DNA probes all of which are tightly linked to the CF gene. 17 of the families had an affected child with, and 24 had one without, meconium ileus. In all cases, CF segregates with these gene probes; however, those with and those without meconium ileus differed in haplotype for CF chromosomes with respect to pJ3.11, which suggests that because of multiallelism (different mutations of the same locus) some CF patients present with meconium ileus and others do not.

Alleles↗
PubMedDate not supplied

Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.

Hypophosphatasia is an inherited disorder characterised by defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 13 European families affected by perinatal, infantile or childhood hypophosphatasia. Eighteen distinct mutations were found, only three of which had been reported previously in North American and Japanese populations. Most of the 15 new mutations were missense mutations, but we also found two mutations affecting donor splice sites and a nonsense mutation. A missense mutation in the last codon of the putative signal peptide probably affects the final maturation of the protein. Despite extensive sequencing of the gene and its promotor region, only one mutation was identified in two cases, one of which was compatible with a possible dominant effect of certain mutations and the putative role of polymorphisms of the TNSALP gene. In 12 of the 13 tested families, genetic diagnosis was possible by characterisation of the mutations or by use of polymorphisms as genetic markers. Hypophosphatasia diagnosis was assigned in two families where clinical, laboratory and radiographic data were unclear and prenatal diagnosis was performed in one case. The results also show that severe hypophosphatasia is due to a very large spectrum of mutations in European populations with no prevalent mutation and that genetic diagnosis of the disease must be performed by extensive analysis of the gene.

Alkaline Phosphatase↗