Previous studies, as early as 1984, have demonstrated the efficiency of maternal serum markers to screen for Down syndrome. These markers were AFP, hCG, oestriol and beta-1-glycoprotein. A pilot study was initiated in France in 1990 to... more
Previous studies, as early as 1984, have demonstrated the efficiency of maternal serum markers to screen for Down syndrome. These markers were AFP, hCG, oestriol and beta-1-glycoprotein. A pilot study was initiated in France in 1990 to evaluate these markers. It lasted from May 1990 until April 1991. 22,410 pregnancies were monitored in total, and 19,407 for women between 30 and 37 years of age. The pregnancy outcome was known for 20,151 cases (86.6%). Sensitivity and predictive value of the test was calculated on 17,362 dosages which outcome was known. The sensitivity based on hCG only was 59.4% (38/64) for trisomy 21 and positive predictive value 1.65% (38/2,307). This test is a better marker than maternal age. In the pilot study it induced a 13.2% rate of amniocentesis. If the risk was calculated using both hCG and AFP results, the performances of the test were better. At equal rate of amniocentesis, the double test increases the sensitivity (+9.5% at risk 1/200, +7% at risk 1/25...
Research Interests: Obstetrics, Medicine, Down Syndrome, Pregnancy, Pubmed, and 4 moreAneuploidy, Amniocentesis, Trisomy 21, and Gynecology
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Research Interests: Medicine and Gynecology
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Objective: To collect data on the practices of molecular genetic testing (MGT) laboratories for the development of national and international policies for quality assurance (QA). Methods: A web-based survey of MGT laboratory directors (n... more
Objective: To collect data on the practices of molecular genetic testing (MGT) laboratories for the development of national and international policies for quality assurance (QA). Methods: A web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on 3 continents. QA and reporting indices were developed and calculated for each responding laboratory. Results: Laboratory setting varied among and within countries, as did qualifications of the directors. Respondents in every country indicated that their laboratory receives specimens from outside their national borders (64%, n = 529). Pair-wise comparisons of the QA index revealed a significant association with the director having formal training in molecular genetics (p < 0.005), affiliation with a genetics unit (p = 0.003), accreditation of the laboratory (p < 0.005) and participation in proficiency testing (p < 0.005). Research labs had a lower mean report score compared to all other settings (...
Research Interests: Genetics, Molecular Biology, Electronics, Informed Consent, International Cooperation, and 15 moreAccreditation, Public Health, Molecular Genetics, Medicine, Humans, Public Health Genomics, Genetic Testing, Medical Biotechnology, Data Collection, Community genetics, Confidentiality, Proficiency testing, Clinical Sciences, Public health systems and services research, and Indexation
The article presents the results of a 4‐month‐period survey by questionnaire among all women attending the Marseille Centre for Prenatal Diagnosis for amniocentesis. Socio‐cultural status of women getting access to amniocentesis is... more
The article presents the results of a 4‐month‐period survey by questionnaire among all women attending the Marseille Centre for Prenatal Diagnosis for amniocentesis. Socio‐cultural status of women getting access to amniocentesis is significantly higher than in the general population of pregnant women in the same geographic area of south‐eastern France. Sociocultural status is also higher among women who have to cover costs of procedure to get access to amniocentesis than among those who benefit from it free‐of‐charge according to French Social Security regulations. In contrast, risk perception and attitudes toward termination of pregnancy are similar in these two groups. A total of 24·4 per cent of respondents declared that they got access to amniocentesis ‘on their own initiative’, the remaining 75·6 per cent declaring that they ‘were following medical advice’. Multidimensional analysis shows that the women who do not benefit from free‐of‐charge amniocentesis, and who have a high l...
Research Interests: Culture, Medicine, France, Pregnancy, Humans, and 15 moreFemale, Amniocentesis, Clinical Sciences, Adult, Pregnant Women, Educational Status, Prenatal Diagnosis, Parity, Gestational Age, Chromosome Disorders, Occupations, Personal autonomy, Patient selection, Chromosome aberrations, and Paediatrics and reproductive medicine
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Research Interests: Clinical Epidemiology, Medicine, France, Abortion, Drug, and 15 moreItaly, Drug Use, Humans, Mathematical Sciences, Female, Clinical, Great Britain, Congenital Anomalies, Adult, Congenital malformation, Chi Square Distribution, First Trimester, Drug Utilization, Medical and Health Sciences, and Drug utilization review
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The Rubinstein-Taybi syndrome (RTS) is a well-defined entity characterized by growth and mental retardation, broad thumbs and halluces, and typical face. The RTS locus was assigned to 16p13.3, and interstitial submicroscopic deletions of... more
The Rubinstein-Taybi syndrome (RTS) is a well-defined entity characterized by growth and mental retardation, broad thumbs and halluces, and typical face. The RTS locus was assigned to 16p13.3, and interstitial submicroscopic deletions of this region (RT1 cosmid, D16S237) were initially identified in 25% of RTS patients. The gene for the human CREB binding protein, the transcriptional coactivator CBP, is included in the RT1 cosmid, and mutations in CBP have recently been identified in nondeleted RTS patients. We investigated 30 French patients with RTS. Among these patients, 3 had the RT1 microdeletion (frequency 10%). There is no obvious phenotypic difference between the patients with and without the RT1 deletion. The RT1 probe appears useful for confirmation of the diagnosis but is of little interest as a screening tool. By pooling data including the previous series and our current series, the cumulative frequency of the 16p13.3 microdeletion is 11.9% (19 in 159). This frequency of approximately 12% deleted patients appears more accurate than the 25% previously reported. Molecular investigations of CBP are in process in our series to clarify the cause of RTS.
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International audienceContributing reviewersThe Editors of Orphanet Journal of Rare Diseases would like to thank all our reviewers who have contributed to the journal in volume 8 (2013)
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We present a method for creating mappings between the Orphanet terminology of rare diseases and the Unified Medical Language System (UMLS), in particular the SNOMED CT, MeSH, and MedDRA terminologies. Our method is based on: (i)... more
We present a method for creating mappings between the Orphanet terminology of rare diseases and the Unified Medical Language System (UMLS), in particular the SNOMED CT, MeSH, and MedDRA terminologies. Our method is based on: (i) aggressive normalisation of terms specific to the Orphanet terminology on top of standard UMLS normalisation; (ii) semantic ranking of partial candidate mappings in order to group similar mappings and attribute higher ranking to the more informative ones. Our results show that, by using the aggressive normalisation function, we increase the number of exact candidate mappings by 7.1-9.5% compared to a mapping method based on MetaMap. A manual assessment of our results shows a high precision of 94.6%. Our results imply that Orphanet diseases are under-represented in the aforementioned terminologies: SNOMED CT, MeSH, and MedDRA are found to contain only 35%, 42%, and 15% of the Orphanet rare diseases, respectively.
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Walker-Warburg syndrome is a congenital malformation syndrome of unknown etiology which is characterized by fatal neurological lesions. It was first described by Walker in 1942 as involving agyria, hydrocephalus and eye malformations. Its... more
Walker-Warburg syndrome is a congenital malformation syndrome of unknown etiology which is characterized by fatal neurological lesions. It was first described by Walker in 1942 as involving agyria, hydrocephalus and eye malformations. Its etiology has been discussed in all of the articles on the subject in the literature, but the majority of the authors describe it as an autosomal recessive syndrome. Ultrasonography plays a key role in detecting a cephalic anomaly by prenatal diagnosis as in our 2 cases. The aim of this article is to report 3 new cases of Walker-Warburg syndrome in two families. Knowledge of this syndrome emphasizes both the need for ultrasonographic observation and genetic counselling for families at risk.
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A set of descriptors was developed and used to code patients with 4p or 9p monosomy or trisomy, “blind” as to their karyotype. Techniques of numerical taxonomy were used to classify the patients on the basis of their phenotypic... more
A set of descriptors was developed and used to code patients with 4p or 9p monosomy or trisomy, “blind” as to their karyotype. Techniques of numerical taxonomy were used to classify the patients on the basis of their phenotypic resemblance. As expected, the results confirm strong phenotype‐karyotype correlations. When cytogenetic interpretations are uncertain, the phenotypic findings may confirm or refute the interpretations. The approach has practical implications, providing further knowledge of phenotypic effects of specific chromosomal segments, which will aid cytogeneticists in their search for karyotypic defects. More important, the results also serve as an excellent model for developing strategies for the classification of syndromes of unknown etiology.
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Short trunk dwarfism involving skeletal anomalies of vertebrae and ribs have been reported under various names. Both dominant and recessive and severe and mild conditions are found. We report on a patient without a severe handicap by age... more
Short trunk dwarfism involving skeletal anomalies of vertebrae and ribs have been reported under various names. Both dominant and recessive and severe and mild conditions are found. We report on a patient without a severe handicap by age 3 years despite severe involvement of the thorax at birth, suggesting that a more complete classification of such anomalies is needed for counseling. We have used an objective method to classify 39 informative patients from the literature, 35 said to have a recessive disease and four a dominant one. Two patients with the costovertebral segmentation defect with mesomelia (COVESDEM) syndrome were added for comparison with our patient. The results of cluster analysis show that there are three phenotypic groups of patients. Cluster 1 contains 19 patients with a severe form of spondylothoracic dysplasia; cluster 2 includes patients with a mild autosomal recessive and a dominant type; cluster 3 groups the two sibs with the COVESDEM syndrome and our patien...
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SummaryWomen under 25 years at the birth of a child with trisomy 21 (Down syndrome) appear to have an increased risk of having another child with a trisomy. If the risk of recurrence is due solely to an increased production of trisomic... more
SummaryWomen under 25 years at the birth of a child with trisomy 21 (Down syndrome) appear to have an increased risk of having another child with a trisomy. If the risk of recurrence is due solely to an increased production of trisomic conceptions, women with an affected child should have a rate of spontaneous abortion higher than average, since the majority of aneuploid conceptuses are expected to be aborted. We examined fetal loss rates among the other pregnancies of 545 women delivered of a child with trisomy 21 and compared the observed loss rates with those which would be expected were the relative risk for these women for an aneuploid recognized pregnancy the same as their relative risk for an aneuploid livebirth as reported by others. Overall loss rates in their prior pregnancies were greatest for women who were 20–24 years old at the time of birth of the proband. Moreover, the observed rate of fetal loss for this group of women (33·8%) was at least as high as that predicted ...
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Prenatal diagnosis (PND) is very developed in France, especially in the area of ultrasound (US) screening. The activity is regulated by law, and laboratories have to be authorized to perform any type of prenatal biological test if the... more
Prenatal diagnosis (PND) is very developed in France, especially in the area of ultrasound (US) screening. The activity is regulated by law, and laboratories have to be authorized to perform any type of prenatal biological test if the purpose is to diagnose fetal defects. There are 70 cytogenetics laboratories and 50 biochemistry laboratories performing serum marker screening, about half of them being private. PND of chromosomal anomalies is offered to women over 37 years of age, to women who already had a child with a chromosomal anomaly, in case of abnormal US findings, if one of the parents has a balanced chromosomal anomaly and if the risk of chromosomal anomaly is higher than 1:250 according to the serum markers. Half of the trisomy 21 cases are now detected prenatally and pregnancies terminated. Fetal cell sampling is performed by amniocentesis in 70% of cases, by chorionic villus sampling in 7% of cases and by fetal blood sampling in 23% of cases. There are no professional guidelines and no quality assessment networks for any of the techniques in use. PND is regulated by two major laws: the Law on Abortion (1975) and the Law on Bioethics (1994).
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Marshall-Smith syndrome is characterized by accelerated skeletal maturation, failure to thrive and dysmorphic features. Since 1971, twenty cases of MSS have been reported. We describe another patient with a very early death demonstrating... more
Marshall-Smith syndrome is characterized by accelerated skeletal maturation, failure to thrive and dysmorphic features. Since 1971, twenty cases of MSS have been reported. We describe another patient with a very early death demonstrating the clinical variability of the syndrome and the importance of systematic X rays of the skeleton for determining the causes of fetal or neonatal death.
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Research Interests: Obstetrics, Risk, Medicine, France, Abortion, and 9 moreDown Syndrome, Canada, Pregnancy, Humans, Female, Pubmed, Trisomy 21, Adult, and Maternal Age
The article presents a cost-benefit analysis of amniocentesis for detection of chromosomal anomalies based on data (1985/87) collected in the Marseille area. In this geographic area, it is possible to confront, in an exhaustive manner,... more
The article presents a cost-benefit analysis of amniocentesis for detection of chromosomal anomalies based on data (1985/87) collected in the Marseille area. In this geographic area, it is possible to confront, in an exhaustive manner, pregnant women's access to amniocentesis and incidence of fetal anomalies due to chromosomal aberrations. Results show that prenatal diagnosis is highly cost-beneficial, the average cost of one "avoided" case of Down's syndrome being lower than the lifelong costs of care for such a child. However, the study emphasizes that the cost-benefit ratio is highly sensitive to the implicit value society affects to the loss of "normal" fetuses through spontaneous abortions provoked by amniocentesis and because of terminations of pregnancy following diagnosis of minor fetal anomalies. The study also shows that lowering maternal age limit for access to free-of-charge amniocentesis from the current 38 years of age to 35 would have been ...
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We surveyed genetics professionals, patients, and the public about rights to information, to requested services, and to parenthood, posing difficult cases found in practice. In all, 2906 genetics professionals (63%), 499 primary care... more
We surveyed genetics professionals, patients, and the public about rights to information, to requested services, and to parenthood, posing difficult cases found in practice. In all, 2906 genetics professionals (63%), 499 primary care physicians (59%), 476 North American genetics patients (67%), 394 French patients (51%), 593 German patients (65%), and 988 members of the American public (99%) returned anonymous questionnaires. Results suggest a trend toward increased respect for patient autonomy since an earlier survey in 1985; in most nations more would perform prenatal diagnosis for a couple with 4 daughters who desire a son. A minority (35% in U.S., 14% elsewhere) would perform PND for a deaf couple who want a deaf child, but most (94% in U.S., 62% elsewhere) would do prenatal paternity testing in the absence of rape or incest. About half (51%) would support a woman with fragile X who wants children. The trend to respect patient autonomy was greatest in the U.S. and was least evid...
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ABSTRACT • All genetic diseases are individually rare but collectively are frequent, so justifying a Public Health approach • Research on genetic diseases requires collaboration between teams from different disciplines and access to data... more
ABSTRACT • All genetic diseases are individually rare but collectively are frequent, so justifying a Public Health approach • Research on genetic diseases requires collaboration between teams from different disciplines and access to data and biological material gathered at International level to ensure adequate sample size • Research and development was unattractive for Industry, as the rarity of the diseases implies a restricted potential market, until a specific regulation in the USA (1983) and in the EU (1999) provided a set of incentives to convince Industry to invest. Orphan drugs for rare diseases now represent 20% of all innovative products. • The development of European collaboration for the delivery of health care and medical services in the field of rare diseases has major potential for bringing benefits to European citizens as no single country can provide the full range of expertise to its citizens • Easily accessible and validated information is a key element to improve quality of health care delivery. Orphanet, the European portal of rare diseases and orphan drugs, has been set up to provide information on each rare disease and on the relevant health care services in Europe and surrounding countries, based on the assumption that, not only are these diseases rare, but the experts are rare as well. All this information is freely accessible on the website http://www.orpha.net KeywordsRare diseases-Genetic diseases-Policy-Public health-Database-Information Technology-Europe