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Biomedical subjects

M P Roth

Publications and source records attributed to M P Roth.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prevalence of neural tube defects in northeastern France, 1979-1994. Impact of prenatal diagnosis.

The objective of this study was to determine in total prevalence of neural tube defects (NTD) in northeastern France during 1979-1994 inclusive, the impact of prenatal diagnosis on birth prevalence. All births and termination of pregnancy affected by NTD were ascertained from multiple sources thank to our registry of congenital anomalies. In our region maternal serum alpha-fetoprotein screening is not available whereas routine ultrasonographic screening of congenital anomalies is performed in all pregnant women. Total prevalence of NTD during 1979-1994 was 10.73 per 10,000 with no upward or downward trend. The total prevalence of NTD in our region remained stable. However birth prevalence fell significantly. The fall was 100 per cent for anencephaly and 60 per cent for spina bifida. This birth prevalence was unchanged for encephalocele. This decrease for anencephaly and spina bifida was obtained by routine ultrasonographic examination only and termination of pregnancy. Comparison with similar studies in other countries demonstrated that screening by maternal serum alpha-fetoprotein is needed in our region.

Female↗
PubMed1997

Congenital eye malformations in 212,479 consecutive births.

Congenital eye malformations were studied in a small geographical area in 212,479 consecutive births. For each of the 145 new cases studied during the period 1979 to 1994, more than 50 factors were compared in probands and in controls. The prevalence rate of congenital eye malformations was 6.8 per 10,000 for microphthalmia 1.7, anophthalmia 0.23, cataract 2.7 and coloboma 1.4 respectively. Sex ratio was 0.82. Prenatal diagnosis was performed in 18 cases and 7 cases were induced abortions. The more common types of associated malformations in the 81 affected cases (53.8%) with at least one anomaly other than an eye malformation were clubfeet, microcephaly, hydrocephaly, cleft lip/palate and facial dysmorphia. At birth infants with eye malformations and other malformations were smaller, weighted less and their head circumference was lower than in controls. Placental weight was also lower than in controls. Pregnancies with eye malformations were more often complicated by threatened abortion, oligoamnios and polyhydramnios. Mothers of children with congenital eye malformations took more often drugs during pregnancy than mothers of controls. Fathers of children with congenital eye malformations were more often exposed to occupational hazards than fathers of controls. There was a significant association between eye malformations and consanguinity of parents. The recurrence risk for first degree relatives of probands was 8.9%. First degree relatives of probands had more than three times the prevalence of non-eye malformations than controls. These results are of relevance to genetic counseling.

Adult↗
PubMed1997

Risk factors in congenital anal atresias.

Congenital anal atresias were studied in a small geographical area in 225,752 consecutive births. For each of the 108 new cases studied during the period 1979 to 1995, more than 50 factors were compared in probands and in controls. The prevalence rate of congenital anal atresias was 4.8 per 10,000 births. Sex ratio was 0.96. Prenatal diagnosis was performed in 14 cases and 11 cases were induced abortions. The more common types of associated malformations in the 45 non syndromic affected cases with at least one major anomaly other than anal atresia were renal agenesia, genital anomalies and ventricular septal defect. At births infants with anal atresia and other malformations were smaller, weighted less and their head circumference was lower than in controls. Placental weight was also lower than in controls. Pregnancies with anal atresia were more often complicated by threatened abortion, oligoamnios and polyhydramnios. Mothers of children with congenital anal atresia took more often drugs during pregnancy than mothers of controls. Fathers of children with anal atresia were more often exposed to occupational hazards than fathers of controls. There was a significant association between anal atresia and consanguinity of parents (p < 0.05). The recurrence risk for first degree relatives of probands was 3.7%. First degree relatives of probands had more than twice the prevalence of non-anal atresia malformations than controls.

Adult↗
PubMed1996

Evaluation of prenatal diagnosis of congenital gastro-intestinal atresias.

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. That an increasing number of fetal anomalies may be detected on prenatal ultrasound is beyond doubt. However what is theoretically possible is not, always done in practice specially when gastrointestinal atresias (GIA) are concerned and when whole antenatal populations are screened rather than high risk groups. Thanks to our registry of congenital anomalies a retrospective study was undertaken to evaluate the prenatal detection of GIA by ultrasound scan in 118,265 consecutive pregnancies of known outcome. Only 31 out of 129 malformed fetuses with GIA were detected (24.0%). The sensitivity of detection varied from 51.4% for atresia of the small intestine to 24.2% for esophageal atresia and 8.2% for ano-rectal atresia. No isolated case with esophageal atresia and ano-rectal atresia were diagnosed. Our results stress the need to perform scans at > or = 18 weeks gestation and to train sonographers in order to improve prenatal detection of GIA.

Adult↗
PubMed1995

The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide sequence and structural characterization.

Human myelin oligodendrocyte glycoprotein (MOG), a myelin component of the central nervous system, is a candidate target antigen for autoimmune-mediated demyelination. We have isolated and sequenced part of a cosmid clone that contains the entire human MOG gene. The primary nuclear transcript, extending from the putative start of transcription to the site of poly(A) addition, is 15,561 nucleotides in length. The human MOG gene contains 8 exons, separated by 7 introns; canonical intron/exon boundary sites are observed at each junction. The introns vary in size from 242 to 6484 bp and contain numerous repetitive DNA elements, including 14 Alu sequences within 3 introns. Another Alu element is located in the 3'-untranslated region of the gene. Alu sequences were classified with respect to subfamily assignment. Seven hundred sixty-three nucleotides 5' of the transcription start and 1214 nucleotides 3' of the poly(A) addition sites were also sequenced. The 5'-flanking region revealed the presence of several consensus sequences that could be relevant in the transcription of the MOG gene, in particular binding sites in common with other myelin gene promoters. Two polymorphic intragenic dinucleotide (CA)n and tetranucleotide (TAAA)n repeats were identified and may provide genetic marker tools for association and linkage studies.

Base Sequence↗
PubMed1995

Evaluation of routine prenatal diagnosis by a registry of congenital anomalies.

Prenatal diagnosis performed by ultrasound scan is now a routine part of prenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In a previous study (Prenat. Diagn., 12, 263-270, 1992), considering the period 1979-1988, we have shown that prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. In 1991 and 1992, the percentage of termination for Down syndrome was 44.4 and 41.9 per cent, respectively. From 1989 to 1992, the detection rate and the specificity of prenatal diagnosis by ultrasonographic examination were improved. The detection rate for isolated malformations (fetuses with only one anomaly) and for multiple malformed children was 26.2 and 66.0 per cent, respectively. The detection rate of congenital anomalies by ultrasonography was variable for the different categories of malformation. A high detection rate was observed for anencephaly (100 per cent) and urinary tract malformation. A low detection rate was seen for cleft lip (17.5 per cent) and limb reduction defects (18.2 per cent).

Abnormalities, Multiple↗
PubMed1995

Polymorphic tri- and tetranucleotide repeats in exons 1 and 8 of the myelin oligodendrocyte glycoprotein (MOG) gene.

Polymorphic (CTC)n and (TAAA)n sequences were identified in exons 1 and 8 of the myelin oligodendrocyte glycoprotein (MOG) gene. The different alleles were detected by a method combining fluorescence labeling of polymerase chain reaction (PCR) products and use of an automated DNA sequencer. Although only two alleles differing by the number of leucine residues encoded by the (CTC)n array were detected at the first locus, seven alleles were identified at the second. The high degree of polymorphism (75%) of the tetranucleotide repeat makes this marker informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis.

Alleles↗
PubMed1995

Prenatal detection of internal urinary system's anomalies. A registry-based study.

Prenatal diagnosis performed by ultrasound scan is now a routine part of antenatal care in our region. How many fetal anomalies are actually detected by this procedure? We have used our registry of congenital malformations to answer this question regarding to Internal Urinary System (IUS) anomalies. The mean time of detection of IUS anomalies was 29 weeks of pregnancy (12-39). The sensitivity of prenatal diagnosis of IUS anomalies by ultrasonographic examination was 59.3% for isolated malformations (fetuses with only one anomaly) and 46.0% for multiple malformed children with IUS anomalies. For all cases of IUS anomalies the percentage of prenatal detection was 56.0. Termination of pregnancy was performed in 9.4% of the cases.

Female↗
PubMed1995

Myelin oligodendrocyte glycoprotein (MOG) gene polymorphisms and multiple sclerosis: no evidence of disease association with MOG.

The region surrounding the myelin oligodendrocyte glycoprotein (MOG) gene, located telomeric to the major histocompatibility complex on chromosome 6, was shown to contain three highly informative microsatellites. To examine the potential role of variants of the MOG gene in susceptibility to multiple sclerosis, these CA-repeat polymorphic markers were characterized on a sample of 169 multiple sclerosis patients and 173 healthy unrelated individuals by a method combining fluorescence labelling of PCR products and use of an automated DNA sequencer. Both patients and controls lived in the southwest of France (in the Pyrénées-Atlantiques) and had similar ethnic background. The distribution of the MOG haplotypes was not significantly different in the two groups (P = 0.38). This is not in favour of the implication of the MOG gene in the genetic component of multiple sclerosis, unless different independent mutations have occurred within this gene.

Base Sequence↗
PubMed1995

Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F. Characterization and relation to HLA haplotypes.

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFc109A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy-Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.

B-Lymphocytes↗
PubMed1995

Prevalence of neural tube defects in northeastern France, 1979-1992 impact of prenatal diagnosis.

The objective of this study was to determine in total prevalence of neural tube defects (NTD) in northeastern France during 1979-1992 inclusive, the impact of prenatal diagnosis on birth prevalence. All births and termination of pregnancy affected by NTD were ascertained from multiple sources thank to our registry of congenital anomalies. In our region maternal serum alpha-fetoprotein screening is not available whereas routine ultrasonographic screening of congenital anomalies is performed in all pregnant women. Total prevalence of NTD during 1979-1992 was 10.94 per 10,000 with no upward or downward trend. The total prevalence of NTD in our region remained stable. However birth prevalence fell significantly. The fall was 100 per cent for anencephaly and 60 and 50 per cent for spina bifida and encephalocele, respectively. This decrease was obtained by routine ultrasonographic examination only and termination of pregnancy. Comparison with similar studies in other countries demonstrated that screening by maternal serum alpha-fetoprotein is needed in our region.

Evaluation Studies as Topic↗
PubMed1994

[Genetics of autoimmune diseases].

Strategies for studying the genetics of autoimmune diseases have undergone a considerable evolution during the last years, especially due to molecular biology techniques and to systematic genome studies. Genetic factors account for 20 to 40% of the risk, and environmental elements play a major role. The major histocompatibility complex comprising HLA genes remains the immunogenetic system most studied and most closely associated with various autoimmune diseases. These associations are mainly observed with HLA class II genes polymorphisms; the precise knowledge of their structure has allowed to define HLA sequence polymorphisms which are themselves risk markers: specific combinations of HLA-DQA and DQB alleles in insulin-dependent diabetes mellitus or a given DR, DQ haplotype for multiple sclerosis. No strong association with HLA-DP has been demonstrated. In all cases the genes involved have a normal structure and the disease is secondary to the combination of a given set of genes with environmental factors. The present knowledge of insulin-dependent diabetes mellitus and multiple sclerosis genetics is rather advanced. Other genes of the HLA region might also be involved in the genetic susceptibility. Results about other immunogenetic systems (T cell receptor genes or heavy chain immunoglobulin genes) are still contradictory but no major gene for autoimmune susceptibility seems to exist in these regions; however autoimmune diseases are under polygenic control; susceptibility genes shared between different diseases often occurring within the same families (Graves' disease and insulin-dependent diabetes mellitus) and genes specific for a given disease (insulin gene region in diabetes) both exist. The present rapid progress in this area is due to the use of highly polymorphic markers randomly distributed across the genome (microsatellites being most informative) and that of animal models: the list of "candidate genes or regions" potentially involved in the genetics of autoimmune diseases is enlarging; the development of coordinated epidemiological studies of molecular genetics along with the sharing of biological resources between different teams allow to build up powerful informative studies which will confirm or refute those "candidates". However, once the list of genes involved is established their mechanism of action will still take time to elucidate.

Autoimmune Diseases↗
PubMed1994

Evaluation of prenatal diagnosis of limb reduction defects by a registry of congenital anomalies.

Prenatal diagnosis performed by ultrasound scan is now a routine part of antenatal care in our region. How many fetal anomalies are actually detected by this procedure? We have used our registry of congenital malformations to answer this question regarding limb reduction defects (LRDs). The mean time of detection of LRDs was 26 weeks of pregnancy (range 16-32 weeks). The sensitivity of prenatal diagnosis of LRDs by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiply malformed children with LRDs, 4.0 and 18.2 per cent, respectively. For all cases of LRDs, the percentage of prenatal detection was 11.5. Termination of pregnancy was performed in 6.7 per cent of the cases.

Congenital Abnormalities↗
PubMed1994

Tumor necrosis factor polymorphism in multiple sclerosis: no additional association independent of HLA.

In order to investigate whether genes coding for tumor necrosis factors (TNF) contribute to the pathogenesis of multiple sclerosis (MS) and also whether they have a non-random association with the MS associated HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype, 40 MS patients and their parents were characterized at four polymorphic loci in the region of the TNF genes: a NcoI RFLP and three microsatellites. We were able to determine the parental haplotypes and used those which were not transmitted to the proband as controls. Fifty percent of the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotypes carried the TNFc1-n2-a11-b4 allelic combination in both the patient and the control groups. However, there was no association of any of these TNF polymorphisms with MS, independent of that already described for the class II region. This, with the lack of association of DP alleles with MS, effectively marks the boundaries of the MS associated haplotype.

Alleles↗
PubMed1994

Gender distributions in parents and children concordant for multiple sclerosis.

The family histories of 7,802 multiple sclerosis (MS) patients were reviewed with respect to the familial pattern of the disease and the gender of the affected individuals. These patients joined an epidemiological study following a call for patients on French television and answered a questionnaire with the help of their physician. 170 had an affected parent, providing 72 mother-daughter pairs, 48 mother-son pairs, 37 father-daughter pairs, and 13 father-son pairs. From these data, the maximum likelihood estimate of the female to male ratio is 2.06, which is not different from what could be expected given the ratio of 2:1 usually found among patients. The apparent deficit of father-son concordant pairs probably simply reflects the well-known preponderance of the disease among females.

Adult↗
PubMed1994

Recent trends in the prevalence of Down syndrome in north-eastern France.

Examination of data from our regional registry of congenital anomalies indicated that 217 children with Down syndrome (DS) were registered (liveborn, stillborn or termination of pregnancy) to mothers living in the Strasbourg area from 1980 to 1992 inclusive. This represents a period prevalence of 1.25 per 1000 total births. From 1980 to 1987, 93 children with DS were registered (prevalence of 0.79 per 1000) whereas from 1988 to 1992, 124 trisomic 21 were identified (prevalence of 1.81 per 1000). In our country since 1980, prenatal diagnosis is offered, free of charge, to all women being 38 years old or more. The percentage of women in whom prenatal diagnosis was performed was "en plateau" since 1986, around 60 per cent. No screening program based on detection of markers in maternal serum (AFP, hCG, U3) is available in our region. A changing pattern of risk in relation to maternal age was identified. In the general population, women under 35 years gave births to 91.7 per cent of all children in 1986 and to 81.1 per cent of all children in 1990. From 1980 to 1987 34.7 per cent of the children with DS were registered in mothers older than 35 years of age, from 1988 to 1992 this percentage was 46.3. From 1982 to 1987, 33 DS were born alive from mothers over 35 years whereas from 1988 to 1992, 25 livebirths DS were born from mothers over 35 years although interruption of DS pregnancies was more frequent in women older than 35 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Down Syndrome↗
PubMed1993

Evaluation of routine prenatal ultrasound examination in detecting fetal chromosomal abnormalities in a low risk population.

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. We have used our registry of congenital malformations to determine how many fetal anomalies and consequently how many chromosomal abnormalities are detected by this procedure. In our region, evaluation of prenatal diagnosis of chromosomal abnormalities in women of 38 years and younger (chromosomal prenatal diagnosis is offered to women > or = 38 years) with no personal or familial history of chromosomal anomaly was performed in 119,099 consecutive pregnancies of known outcome from 1980 to 1987. At least one ultrasonographic examination seeking congenital malformations was performed in more than 95% of the pregnant women studied. The total number of chromosomal anomalies during the study period was 199, 123 of these being Down syndrome. Only 41 (34.5%) of the 119 fetuses with chromosomal abnormalities and congenital malformation examined had been found to have a malformation at ultrasound examination. This low sensitivity was different for the diverse chromosomal abnormalities. Only 10 out of the 54 fetuses with Down syndrome and malformations (18.5%) were detected and only 3 out of 24 (12.5%) atrioventricular canal defects in those trisomic 21 patients were detected. Only 5 out of 11 (45.4%) fetuses with trisomy 13, 13 out of 26 (50.0%) fetuses with trisomy 18, 7 out of 12 patients with monosomy X (58.3%) and 6 out of 27 (22.2%) fetuses with other chromosomal abnormalities were diagnosed. Moreover, the time of detection of these anomalies was early enough to allow amniocentesis and termination of pregnancy in the case of a chromosomal abnormality in only 15 out of these 41 patients, including 7 cases of cystic hygroma in fetuses with monosomy X. This low sensitivity is not the result of the quality of the ultrasound equipment. It may be explained by the inadequate qualification of some operators and by the insufficient duration of the routine examination. In conclusion, our study has shown that the sensitivity of the detection of chromosomal abnormalities by routine prenatal ultrasound screening is low. Other screening methods are needed.

Adult↗