Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions

Boué, J; Boué, A; Lazar, Philippe

doi:10.1002/tera.1420120103

Cited by 610 publications

(79 citation statements)

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“…Chromosome imbalance represents, in sum, the major known cause of both abortion (5) and mental retardation (6) in human beings. Down syndrome (trisomy 21) is the most common viable human aneusomy and comprises the majority of individuals who are retarded because of chromosomal imbalance (7).…”

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confidence: 99%

Down syndrome: Gene dosage at the transcriptional level in skin fibroblasts

Kurnit

1979

Proc. Natl. Acad. Sci. U.S.A.

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Chromosome imbalance (aneusomy) is the leading known cause of both spontaneous abortion and mental retardation in human beings. The primary abnormality is thought to result from quantitative changes of transcription products from the unbalanced genetic material. To document this point, I compared chromosome 21-specific transcription in skin fibroblasts from subjects with monosomy 21, disomy 21 (normal), and trisomy 21 (Down syndrome (aneusomy) are shown by the lethality in human beings of monosomy for more than 2-3% and trisomy for more than 5-6% of the haploid autosomal genome (1).Smaller deficiencies and duplications of autosomal material are associated with altered phenotypes which can be recognized by specific patterns of malformation and are usually associated with mental retardation (2-4). Chromosome imbalance represents, in sum, the major known cause of both abortion (5) and mental retardation (6) in human beings. Down syndrome (trisomy 21) is the most common viable human aneusomy and comprises the majority of individuals who are retarded because of chromosomal imbalance (7).The actual mechanism whereby chromosomal imbalance results in major phenotypic effects remains poorly understood. However, several points are clear: (i) The defect is due to quantitative alteration of normal genetic material. This point is best illustrated by a case report of monozygotic twins who are discordant for Down syndrome (8 Given this background, elucidation of the mechanism(s) whereby aneusomy results in metabolic and phenotypic aberrations will require analyses at the primary level of gene action-i.e., transcription. This report describes some first steps toward such an analysis: RNA sequences transcribed from human chromosome 21 are quantitated in skin fibroblasts with one, two, and three copies per genome of chromosome 21. MATERIALS AND METHODSSynthesis of cDNAs. Human skin fibroblasts were grown to confluency in Dulbecco-Vogt medium containing 16% heat-inactivated fetal calf serum, fed, and harvested 4 days later. They were scraped off with a rubber policeman into ice-cold phosphate-buffered saline containing 1:200 (vol/vol) diethylpyrocarbonate (Sigma). The cells were pelleted and resuspended in 5 vol of 5 M guanidine thiocyanate (Tridom), 50 mM Tris-HCl (pH 7.6), 10 mM EDTA, and 5% (vol/vol) 2-mercaptoethanol. Sarkosyl was added to 4% (wt/vol), and 0.5 g of CsCl was added per ml of solution. The solution was layered over a 1-ml cushion of 5.7 M CsCl in 100 mM EDTA and centrifuged in a Spinco SW 50.1 rotor at 35,000 rpm for 12 hr at 20°C (16 2372The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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confidence: 99%

Down syndrome: Gene dosage at the transcriptional level in skin fibroblasts

Kurnit

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, trisomy 21 is a major cause of premature pregnancy failure. It is estimated that 1/150 conceptions have trisomy 21 and that 80% of these are lost during early pregnancy (Boué et al, 1975;Hassold and Jacobs, 1984;Freeman et al, 1991); The nondisjunction event that results in two copies of chromosome 21 takes place in anaphase of meiosis I during oocyte maturation before ovulation, and/or in anaphase of meiosis II around the time of fertilization in the adult female (Ramírez et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China

Wang

Qiao

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78~8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90~14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058~17.496). The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

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“…Over the past 40 years, or even more, there have been performed only a few large-scale studies in which the number of karyotype sample from missed abortions exceeded 1,000 specimen of non-developing products of concept [1][2][3][4]. While these studies were carried out at different times in different countries and populations, in all of them trisomy prevailed in the structure of chromosomal abnormalities found in missed pregnancies, with its portion varying from 44 to 66 % ( Table 1).…”

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confidence: 99%

The Rare Regular Trisomy 17: Frequency and Phenotypic Portrait

Veropotvelyan

2017

EUREKA: Health Sciences

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This paper presents the data from our own research of frequency of full regular trisomy 17 (T17) based on 1808 samples of miscarriages, 1572 medical induced abortions at 5-11 weeks of gestation, and 9689 samples of invasive prenatal tests done between 11 and 24 weeks of pregnancy. The frequency of full T17 in all miscarriages was 1/152 and in medical induced abortions - 1/524; the population frequency of T17 in the first trimester accounted for 1/454. Additionally, it presents the data on the proportion of T17 of all autosomal trisomies structure in different periods of fetal development. When performing invasive prenatal testing we detected 4 cases of T17 that represented 0, 58 % of autosomal trisomies among fetuses of 11-22 gestational weeks. Furthermore, the paper introduces a symptom-complex of fetal abnormalities that are typical of regular full trisomy 17.

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Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions

Cited by 610 publications

References 12 publications

Down syndrome: Gene dosage at the transcriptional level in skin fibroblasts

Down syndrome: Gene dosage at the transcriptional level in skin fibroblasts

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China

The Rare Regular Trisomy 17: Frequency and Phenotypic Portrait

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