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Biomedical subjects

A Boué

Publications and source records attributed to A Boué.

At least 19 recordsLinked to original sources
PubMed1994

Maternal serum free beta hCG screening: results of studies including 480 cases of Down syndrome.

The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2.64, significantly greater than the reported median MOM of intact hCG (p < 0.0001). In 234 of these cases from retrospective and prospective studies, the effectiveness of maternal serum free beta hCG was evaluated in combination with alpha-fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening. Down syndrome detection in the gestational age range of 14-16 weeks was 82 per cent. In all gestational weeks (14-22), a 77.7 per cent Down syndrome detection rate was achieved. In prospective screening of 44,272 patients under the age of 35 years, 69 per cent of Down syndrome cases were detected (73 per cent in gestational weeks 14-16). The false-positive rate for the prospective study was 3.8 per cent. The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening population (i.e., women under 35 years) yields an improved detection efficiency over other protocols.

Adult↗
PubMed1994

Do racial differences exist in second-trimester maternal hCG levels? A study of 23,369 patients.

In Down syndrome screening by maternal serum human chorionic gonadotropin (hCG) determination at 15, 16, 17, and 18 weeks of gestation, we prospectively examined 23,369 sera from white (21,549), North African (970), black African (525), and Asian (325) patients. When expressed as multiples of the median (MOM), no difference was observed between white, North African, and black African patients. However, higher serum hCG concentrations were noted in Asians, for whom we therefore recommend correction of hCG values before calculation of the risk of Down syndrome.

Asian People↗
PubMed1993

Molecular analysis of a ring chromosome X in a family with fragile X syndrome.

The phenotypically normal sister of a patient affected by fragile X syndrome was referred for genetic counselling and was found to carry a mosaic karyotype 46,X,r(X)/45,X. Because the probability of the simultaneous chance occurrence of fragile X syndrome and a ring chromosome X in the same family is very low, we postulated that the breakpoint of the ring chromosome X originated in the cytogenetic break in Xq27.3 responsible for fragile X syndrome. In order to determine the relative positions of the breakpoint on the ring chromosome X and the (CGG)n unstable sequence responsible for the fragile X mutation, we used molecular markers to analyse the telomeric regions of chromosome X in this family. The results showed that the ring chromosome X was the maternal fragile X chromosome and that the telomeric deletion on the long arm encompassed the (CGG)n sequence. This suggests that the cytogenetic break in Xq27.3 is distinct from the unstable (CGG)n sequence, or that the break followed by the end-to-end fusion creating the ring chromosome was not completely conservative. Analysis of DNA markers on the short arm of chromosome X evidenced a deletion of a large part of the pseudoautosomal region, allowing us to position the genes involved in stature and in some syndromes associated with telomeric deletions of Xp on the proximal side of the pseudoautosomal region.

Adult↗
PubMed1993

General cystic fibrosis mutations are usually missense mutations affecting two specific protein domains and associated with a specific RFLP marker haplotype.

Some 250 different mutations have so far been screened in the cystic fibrosis (CF) gene. The 50 nonsense, 33 splicing and 60 frameshift mutations are randomly distributed within the gene, unlike the 107 missense mutations or amino acid deletions. A large excess of missense mutations affects the exons encoding the first transmembrane (MS1) and first ATP-binding fold (NBF1) domains. Sixty-four of the 107 missense mutations may be classified as private, demic, local and general mutations on the basis of their geographic distribution in Europe. Private and demic mutations are randomly distributed within the gene; local and general mutations are not. It is well known that some RFLP markers are in linkage disequilibrium with some mutations. Private, demic and local mutations are randomly associated with each class of RFLP haplotypes. In contrast, general mutations, frequent and infrequent, are not randomly associated with RFLP markers. General mutations usually affect a specific part of the gene and are more likely to be associated with a specific RFLP marker. This suggests the existence of selective factors favoring these mutations, a hypothesis formerly postulated as a possible cause of the high frequency of the disease.

Cystic Fibrosis↗
PubMed1993

Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes.

In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragile X chromosomes. Contrary to observations made in myotonic dystrophy, fragile X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. We propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen.

Alleles↗
PubMed1993

[Cost-benefit analysis of prenatal screening for trisomy 21 through analysis of HCG in maternal blood].

Introduction of maternal serum markers for prenatal screening of Down's syndrome implies a redefinition of the criteria used for identifying at risk women for screening by amniocentesis, which are currently based on maternal age. On the basis of the first French prospective study of human chorionic gonadotropin measurement in maternal serum as a predictor of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement was more cost-effective than one relying on maternal age alone. A cost-benefit analysis (using the "avoided" lifelong costs of care for a trisomic 21 child that are allowed by prenatal screening) would justify lower hCG cut-off values and an higher detection rate of Down's syndrome (74.5%) than other decision rules based on alternative principles such as: equalization to 1% of fetal risk of Down's syndrome for access to amniocentesis at all maternal ages or equalization to 1/1000 of fetal risk of Down's syndrome among women not undergoing amniocentesis. However, results of the cost-benefit analysis are very sensitive to other factors such as the cost associated with loss of a normal fetus due to iatrogenic risk of amniocentesis (false positives of hCG). Ethical and value-laden issues that necessarily underlie economic evaluation of screening programmes, as well as other decision rules based on equalization of acceptable risk for each maternal age, are discussed.

Adolescent↗
PubMed1992

Levels and molecular forms of immunoreactive trypsin and chymotrypsin in amniotic fluids from normal and cystic fibrosis fetus: evidence for a lack of activation of proteolytic zymogens in cystic fibrosis fetus.

We previously suggested that an activation defect of pancreatic proteolytic zymogens in newborns suffering from cystic fibrosis (CF) might contribute (by an adaptative-like process) to the significant increase of the serum trypsin level observed in the disease at birth. To give support to this hypothesis we studied two pancreatic enzymes: trypsin 1 (IRT) and chymotrypsin A (IRChT) by noncompetitive enzyme immunoassays in amniotic fluids taken at 17-18 weeks of pregnancy. In normal fluids (102), the levels of the two enzymes were widely dispersed between 5 and 100 micrograms/L. A similar pattern was observed for the fluids with a 1 in 4 risk of CF with a normal outcome (24). In contrast, the levels of pancreatic enzymes in the fluids with affected fetus (40) were always below 45 micrograms/L for IRT and 55 micrograms/L for IRChT and most of them were under 20 micrograms/L for both enzymes. The molecular forms of IRT and IRChT in amniotic fluids were studied by gel filtration. In amniotic fluids with affected fetus, a major form of IRT was eluted in a position consistent with the elution of proteins around 25 kDa and two peaks of IRChT were eluted at 75 kDa and 25 kDa. These patterns are similar to those observed in normal serum when zymogens are present and are quite different from the patterns obtained by gel filtration of amniotic fluids with normal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniocentesis↗
PubMed1992

Molecular studies of a translocated (X;22) DiGeorge patient using somatic cell hybridization.

In order to better characterize the chromosomic rearrangement of an unbalanced 45XX t(X;22) (q28;q11) DiGeorge patient, a somatic hybrid clone segregating the translocated chromosome was constructed and investigated using X and 22 linked markers. Our study demonstrated that this de novo translocation was from paternal origin. The breakpoint was assigned between DXS296 and IDS loci at Xq28 and between D22S9 and BCRL2 at 22q11. This observation and published data allow to locate a "critical region" for DiGeorge syndrome between these two last loci on 22q11. Our hybrid clone may be a useful tool for mapping new probes arising in this region.

Blotting, Southern↗
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

[Strategies for selection of pregnancies with increased risk of fetal trisomy 21].

The main indications for cytogenetic prenatal diagnosis have been based on pregnancies with an increased risk of chromosomal anomaly. Advanced maternal age has been the most important criterion and presently 60% of women of 38 yr and over undergo prenatal diagnosis. Fetal malformations detected by ultrasound resulted in the selection of a group in which approximately 10% chromosomal anomalies were detected. An effort has been made to describe sonographic signs indicative of Down's syndrome. Maternal serum biochemical markers constitute another approach for screening. Human chorionic gonadotropin is the most discriminant test. Combining maternal and hCG cut-off levels, it is possible to detect approximately 70% of trisomy 21% in women aged between 30-38 yr.

Adult↗
PubMed1991

Distribution of deletions and seven point mutations on CYP21B genes in three clinical forms of steroid 21-hydroxylase deficiency.

To characterize mutations in the CYP21B gene that are responsible for congenital adrenal hyperplasia (CAH), DNA samples from 91 French patients have been studied by allelic-specific oligonucleotide hybridization and Southern blot analysis. Seven sites mostly found in the CYP21A pseudogene and deletions of the functional CYP21B gene have been screened. Gene conversions involving small DNA segments accounted for 57% of the tested mutations and probably cause 74% of the mutations responsible for the disease. Complete deletion of the CYP21B gene accounted for 18% of the CAH mutations in the whole sample and for 21% in the classical form of the disease. Three mutations were found associated with specific clinical forms of the disease: a G-C substitution in the seventh exon was associated with the late-onset form of the disease, and both an 8-bp depletion in the third exon and complete deletion of CYP21B were associated with the salt-wasting form.

Adrenal Hyperplasia, Congenital↗
PubMed1990

A single chorionic gonadotropin assay for maternal serum screening for Down's syndrome.

A simple enzyme immunoassay measuring human chorionic gonadotropin in undiluted maternal serum has been developed in order to be used as a prenatal screening test for Down's syndrome. A retrospective study of maternal serum sampled during pregnancies associated with trisomy 21 shows that with a 5% amniocentesis rate determined on a single test, the detection rate of trisomy 21 would be around two-thirds of the affected pregnancies. A prospective study of 9040 pregnant women under 38 years has confirmed the usefulness of the assay.

Adult↗