1/12. A trisomic germ cell line and precocious chromatid segregation leads to recurrent trisomy 21 conception.A chromosomally normal 37-year-old woman was referred for preimplantation genetic diagnosis after having several conceptuses with trisomy 21. Segregation of chromosome 21 was assessed in unfertilised meiosis II oocytes and preimplantation embryos from PGD cycles using fluorescent in situ hybridisation (FISH). Of 7 preimplantation embryos, 5 were chromosomally abnormal with 4 having trisomy 21 and one being tetraploid. Of 4 oocytes, 3 had an abnormal chromosomal constitution with either an extra chromosome 21 or an extra chromatid 21. In one oocyte an extra chromatid 21 was detected in both the metaphase II complement and the first polar body providing the first direct evidence of a maternal trisomic germ cell line. Moreover, this result shows that the extra chromosome 21 can precociously divide into its two chromatids at the first meiotic division.- - - - - - - - - - ranking = 1keywords = conception (Clic here for more details about this article) |
2/12. Recurrent trisomy 21 in a couple with a child presenting trisomy 21 mosaicism and maternal uniparental disomy for chromosome 21 in the euploid cell line.recurrence of trisomy 21 was observed in a family in which both parents had a normal chromosome complement. Mosaic trisomy 21 was found in a blood karyotype of the first child, a second pregnancy ended in spontaneous abortion, and a full trisomy 21 was found at prenatal diagnosis of the third pregnancy of this same couple. Although recurrent trisomy 21 may be due to chance, the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for recurrence risk. Molecular analysis was therefore undertaken in this family to determine the parental origin and the stage of nondisjunction of the extra chromosome 21 in both cases. Although a maternal origin of both instances of trisomy 21 was observed, the mosaic case showed homozygosity for all markers along the duplicated maternal chromosome. Such a finding would normally suggest a postzygotic origin of the trisomy 21. However, the diploid cell line in this same case showed maternal uniparental disomy 21, implying that it was the result of a trisomic conception. We suggest that a somatic nondisjunction in the maternal germ cells is the most likely explanation for these findings. The apparent meiotic II stage of nondisjunction of the nonmosaic trisomy 21 fetus was consistent with maternal mosaicism. A review of the literature for recurrent trisomy 21 cases studied by molecular means, suggests that mosaicism in germ cells may account for more cases than is detected cytogenetically. These results also show that dna marker analysis does not provide a valuable tool for patient counseling in case of recurrent trisomy 21.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
3/12. Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with down syndrome and neural tube defect.The association of neural tube defects (NTDs) with down syndrome (trisomy 21) and altered folate metabolism in both mother and affected offspring provide a unique opportunity for insight into the etiologic role of folate deficiency in these congenital anomalies. We describe here the case of a male child with trisomy 21, cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed homozygosity for the mutant 677C-->T polymorphism in both the mother and child. The plasma homocysteine of the mother was highly elevated at 25.0 micromol/L and was associated with a low methionine level of 22.1 micromol/L. Her s-adenosylhomocysteine (SAH) level was three times that of reference normal women, resulting in a markedly reduced ratio of s-adenosylmethionine (SAM) to SAH and significant dna hypomethylation in lymphocytes. The child had low plasma levels of both homocysteine and methionine and a reduced SAM/SAH ratio that was also associated with lymphocyte dna hypomethylation. In addition, the child had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. We suggest that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21. Altered folate status and homozygous TT mutation in the MTHFR gene in both mother and child would be expected to increase the risk of neural tube defects. The presence of both trisomy 21 and postclosure NTD in the same child supports the need for an extended periconceptional period of maternal folate supplementation to achieve greater preventive effects for both NTD and trisomy 21.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
4/12. Robertsonian translocations--reproductive risks and indications for preimplantation genetic diagnosis.BACKGROUND: Robertsonian translocations carry reproductive risks that are dependent on the chromosomes involved and the sex of the carrier. We describe five couples that presented for preimplantation genetic diagnosis (PGD). methods: PGD was carried out using cleavage-stage (day 3) embryo biopsy, fluorescence in-situ hybridization (FISH) with locus-specific probes, and day 4 embryo transfer. RESULTS: Couple A (45,XX,der(14;21)(q10;q10)) had two previous pregnancies, one with translocation trisomy 21. A successful singleton pregnancy followed two cycles of PGD. Couple B (45,XX,der(13;14)(q10;q10)) had four miscarriages, two with translocation trisomy 14. One cycle of PGD resulted in triplets. Couple C (45,XX,der(13;14)(q10;q10)) had four years of infertility; two cycles were unsuccessful. Couple D (45,XY,der(13;14)(q10;q10)) presented with oligozoospermia. A singleton pregnancy followed two cycles of PGD. Couple E (45,XY,der(13;14)(q10;q10)) had a sperm count within the normal range and low levels of aneuploid spermatozoa. PGD was therefore not recommended. No evidence for a high incidence of embryos with chaotic or mosaic chromosome complements was found. CONCLUSIONS: For fertile couples, careful risk assessment and genetic counselling should precede consideration for PGD. Where translocation couples need assisted conception for subfertility, PGD is a valuable screen for imbalance, even when the risk of viable chromosome abnormality is low.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
5/12. Midline developmental anomalies in down syndrome.Infants with down syndrome are known to have a high frequency of birth defects, particularly cardiac and gastrointestinal defects. Mental retardation of different degrees is common, but accompanying central nervous system malformations are rare. We report a boy born spontaneously in the 37th postconceptional week with multiple malformations: microcephaly, hypertelorism, blepharophimosis, medial cleft palate, micrognathia, omphalocele, and pathologic palmar and plantar creases. Cardial sonography revealed a ventricular septal defect and mild pulmonary stenosis. Cranial magnetic resonance imaging demonstrated a general but infratentorial stressed brain atrophy with widening of the inner and outer cerebrospinal fluid spaces and dysplasia of the corpus callosum. Chromosomal analysis showed a free trisomy 21. The boy had muscular hypotonia and developed severe motor and mental retardation, accompanied by microsomia and generalized epileptic seizures. At age 8 months, he died of sudden nocturnal respiratory and cardiac failure. The peculiarity of this case is the combination of down syndrome with midline developmental defects (callosal dysplasia, medial cleft palate, omphalocele) accompanied by severe malformative encephalopathy. There are no previous reports of this combination, but there are genetic links between down syndrome and midline defects concerning the drosophila single-minded (sim) gene. The expression pattern of the human sim corresponding gene suggests that it might be involved in the pathogenesis of midline defects in down syndrome.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
6/12. prenatal diagnosis of partial trisomy 21 associated with maternal balanced translocation 46xx der 21 t(21q;22q) with pericentric inversion of chromosome 9.This communication reports prenatal diagnosis of partial trisomy 21 resulting from balanced translocation (21q;22q) in a 36-year-old gravida 7, para 1 woman. The lady had only one living child and there was history of recurrent spontaneous first trimester abortions. Triple test was abnormal in the present conception. In addition, the woman had pericentric inversion of chromosome 9, a finding scarcely reported previously with carrier status in Indian literature. A few cytogeneticists consider this as a normal variant. However, many reports in the recent literature link pericentric inversion of chromosome 9 with infertility, recurrent abortions and a number of other abnormal conditions. A review of the relevant literature pertinent to the case is provided.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
7/12. reproduction in a woman with low percentage t(21q21q) mosaicism.The birth of a child is described with down syndrome followed by the conception of a fetus bearing the t(21q21q) chromosome in 100% of their cells in a women mosiac for the translocation in less than 10% of 2 of her examined tissues and in none of the cells in her peripheral blood. Various hypotheses for explaining the above findings are discussed. The importance of examining as many parental tissues as possible for the detection of low percentage mosiacism is stressed.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
8/12. Monozygotic twins with discordant karyotypes: a case report.A monochorionic twin pregnancy had normal male karyotype on chorionic villous sampling. At delivery, one twin presented as morphologically normal, the other as trisomy 21. A twinning event and chromosome division error shortly after conception resulted in monozygotic twins with discordant tissue karyotypes and blood chromosome chimerism for trisomy 21.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
9/12. Neonatal teeth association with Down's syndrome. A case report.A case of natal teeth in a four-day-old female brought by a forty four year old mother is presented. These natal teeth were present in the upper and lower jaws. Of special interest was the shape and positions of these especially the upper tooth in the left canine region and the fact that these teeth were present in a child with Down's syndrome features. The anxiety of the mother and the desire to get them removed immediately underlines the superstition and misconceptions with which natal teeth are viewed. The multidisciplinary approach to management is also highlighted.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
10/12. Difficulty in securing treatment for degenerative hip disease in a patient with down syndrome: the gap remains open.In 2002, the office of the U.S. surgeon general published a report detailing the discrepancies between the quality of healthcare afforded to persons with and without mental retardation. This article examines the case of a female resident of a developmental center with profound mental retardation due to down syndrome and degenerative hip disease. Although she was in urgent need of a total hip replacement, the operation was denied or delayed by several different surgeons. Using a survey of physician attitudes, we examine several possible motivations behind the surgeons' reluctance to perform the procedure and conclude that these reasons were not appropriate in this case. Finally, we reiterate the surgeon general's call to eradicate preconceptions held in the medical community about the population of persons with mental retardation that result in similar failures to provide adequate care.- - - - - - - - - - ranking = 0.25keywords = conception (Clic here for more details about this article) |
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