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Stanley I. Rapoport - One of the best experts on this subject based on the ideXlab platform.
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Altered calcium currents in cultured sensory neurons of normal and Trisomy 16 mouse fetuses, an animal model for human Trisomy 21 (Down Syndrome)
Biological research, 2006Co-Authors: Pablo Caviedes, Raúl Caviedes, Stanley I. RapoportAbstract:Down syndrome is determined by the presence of an extra copy of autosome 21 and is expressed by multiple abnormalities, with mental retardation being the most striking feature. The condition results in altered electrical membrane properties of fetal dorsal root ganglia (DRG) neurons, as in the Trisomy 16 fetal mouse, an animal model of the human condition. Cultured trisomic DRG neurons from human and mouse fetuses present faster rates of depolarization and repolarization in the action potential compared to normal controls and a shorter spike duration. Also, Trisomy 16 brain and spinal cord tissue exhibit reduced acetylcholine secretion. Therefore, we decided to study Ca2+ currents in cultured DRG neurons from Trisomy 16 and age-matched control mice, using the whole-cell patch-clamp technique. Trisomic neurons exhibited a 62% reduction in Ca2+ current amplitude and reduced voltage dependence of current activation at -30 and -20 mV levels. Also, trisomic neurons showed slower activation kinetics for Ca2+ currents, with up to 80% increase in time constant values. Kinetics of the inactivation phase were similar in both conditions. The results indicate that murine Trisomy 16 alter Ca2+ currents, which may contribute to impaired cell function, including neurotransmitter release. These abnormalities also may alter neural development.
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Impaired cholinergic function in cell lines derived from the cerebral cortex of normal and Trisomy 16 mice.
The European journal of neuroscience, 2000Co-Authors: David D. Allen, Raúl Caviedes, Christian Arriagada, Stanley I. Rapoport, Ana María Cárdenas, José Martin, Pablo CaviedesAbstract:Murine Trisomy 16 is an animal model of human Down's syndrome. We have successfully established permanently growing cell lines from the cerebral cortex of normal and Trisomy 16 foetal mice using an original procedure. These lines, named CNh (derived from a normal animal) and CTb (derived from a trisomic foetus), express neuronal markers. Considering that Down's syndrome exhibits cholinergic deficits, we examined cholinergic function in these lines, using incorporation of [3H]-choline and fractional release studies. After 1, 3 and 5 min of [3H]-choline incubation, CTb cell uptake was lower by approximately 50% compared to controls. Hemicholinium-3 significantly reduced the incorporation of [3H]-choline in both CNh and CTb cells at high concentration (10 microM), suggesting high-affinity choline transport. However, CTb cells exhibited greater sensitivity to the blocker. For fractional release experiments, the cells were stimulated by K+ depolarization, glutamate or nicotine. When depolarized, CTb cells showed a 68% reduction in fractional release of [3H]-acetylcholine compared to CNh cell line, and a 45% reduction when stimulated by nicotine. Interestingly, glutamate induced similar levels of release in both cell types. The results indicate the existence of cholinergic dysfunction in CTb cells when compared to CNh, similar to that reported for primary cultures of Trisomy 16 brain tissue (Fiedler et al. 1994, Brain Res., 658, 27-32). Thus, the CTb cell line may serve as a model for the study of Down's syndrome pathophysiology.
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Calcium signals in cell lines derived from the cerebral cortex of normal and Trisomy 16 mice.
Neuroreport, 1999Co-Authors: Ana María Cárdenas, Raúl Caviedes, Stanley I. Rapoport, Maribel P. Rodríguez, Magdalena P. Cortés, Rocío Álvarez, Wei-zheng Wei, Takeshi Shimahara, Pablo CaviedesAbstract:WE established two immortalized cell lines from cerebral cortex of normal (CNh) and Trisomy 16 (CTb) mouse fetuses, an animal model of human Trisomy 21. Those cells loaded with the fluorescent Ca 2+ dyes, Indo-1 and Fluo-3, exhibited increments of intracellular Ca 2+ ([Ca 2+ ] i ) in response to external glutamate, NMDA, AMPA and kainate. CTb cells exhibited higher basal Ca 2+ concentrations and had higher amplitude and slower time-dependent kinetics in the decay than CNh cells, suggesting an impaired Ca 2+ buffering capacity in the Trisomy 16-derived cell line. Nicotine also induced increments of [Ca 2+ ] i . The CTb cell line could represent a model for studying cellular alterations related to Down syndrome.
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in cortical cultures of Trisomy 16 mouse brain the upregulated metallothionein i ii fails to respond to h2o2 exposure or glutamate receptor stimulation
Brain Research, 1998Co-Authors: Marzia Scortegagna, Stanley I. Rapoport, Zygmunt Galdzicki, Ingeborg HanbauerAbstract:Abstract To assess whether a defective oxidative defense may contribute to Down's syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in primary cultures of cerebral cortex from fetal Trisomy 16 mice and their euploid littermates. Western blot analysis showed that MT-I/II was upregulated and the protein carbonyl content was higher in Trisomy 16 compared with euploid cultures. Addition of N-acetyl- l -cysteine to the culture medium reduced the increment of MT-I/II in Trisomy 16 cortical cells. In euploid, but not trisomic cortical cultures, kainic acid, trans-(±)-ACPD, or H2O2 exposure elicited a dose-dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II immunoblot densities were not increased beyond their elevated basal levels. In contrast, 25 μM Pb induced MT-I/II, to a similar extent, in cortical cultures from euploid and Trisomy 16 mice. This suggests that the antioxidant—but not the metal—response element of the MT-I/II promoter was altered by increased oxidative stress. Our data suggest that, in the Trisomy 16 mouse, the effects of increased production of reactive oxygen species, due to the increased SOD-1, GluR5, or amyloid precursor protein gene dosage, is exacerbated by an insufficient or missing antioxidant response.
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Evidence of increased oxidative stress in hippocampal primary cultures of Trisomy 16 mouse. Studies on metallothionein-I/II.
Restorative neurology and neuroscience, 1998Co-Authors: Ingeborg Hanbauer, Zygmunt Galdzicki, Stanley I. Rapoport, Marzia ScortegagnaAbstract:In the Trisomy 16 mouse the increased gene dosage of SOD-1 increases H 2 O 2 production that results in increased oxidative stress. We report here that in hippocampal primary cultures, metallothionein (MT)-I/II immunoreactivity was present mainly in glial fibrillary acidic protein-immunolabeled cells. Western blot analysis showed a two-fold higher level of MT-I/II in Trisomy 16 mice then in euploid littermates. In contrast, the immunoreactivity of glutamine synthetase, another glia-expressed protein, was similar in hippocampal cultures of Trisomy 16 mouse and euploid littermates. Oxyblot analysis of hippocampal cultures showed that the carbonyl content in several protein bands was higher in Trisomy 16 mice than in euploid littermates giving evidence for increased oxidative stress in Trisomy 16 mouse cultures. To evaluate the responsiveness of MT-I/II to agents that increase the level of reactive oxygen species in cells we measured the effect of H 2 O 2 , kainic acid, (±)ACPD, and β-amyloid peptide 1-42. Westem blot analysis documented that in hippocampal cultures of euploid littermates MT-I/II was maximally increased by 50 μM H 2 O 2 , 100 μM kainic acid, 10 μM (±)ACPD, or 1.0 mM β-amyloid peptide 1-42, whereas in those of Trisomy 16 mice no further increase above the elevated level was observed. Our data suggest that in the Trisomy 16 mouse the production of reactive oxygen species may have shifted the intracellular redox environment that could have altered the susceptibility of MT-I/II transcription. The possibility that transcription factors whose activation may be essential to initiate MT-I/II transcription get oxidized has yet to be examined.
Pablo Caviedes - One of the best experts on this subject based on the ideXlab platform.
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Small-molecule aggregation inhibitors reduce excess amyloid in a Trisomy 16 mouse cortical cell line
Biological Research, 2008Co-Authors: Andréa C. Paula Lima, Raúl Caviedes, Pablo Caviedes, Christian Arriagada, Rodrigo Toro, Ana M. Cárdenas, Sergio T. FerreiraAbstract:We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the β-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP) accumulation in the CTb immortalized cell line derived from the cerebral cortex of a Trisomy 16 mouse, an animal model of Down’s syndrome. Compared to a non-trisomic cortical cell line (CNh), CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca 2+ levels ([Ca 2+ ] i ). Here, we show that the compounds 2,4dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca 2+ ] i . Results indicate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells. Key terms: Alzheimer’s disease, Down syndrome, intracellular amyloid, murine Trisomy 16, small molecule inhibitors.
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Altered calcium currents in cultured sensory neurons of normal and Trisomy 16 mouse fetuses, an animal model for human Trisomy 21 (Down Syndrome)
Biological research, 2006Co-Authors: Pablo Caviedes, Raúl Caviedes, Stanley I. RapoportAbstract:Down syndrome is determined by the presence of an extra copy of autosome 21 and is expressed by multiple abnormalities, with mental retardation being the most striking feature. The condition results in altered electrical membrane properties of fetal dorsal root ganglia (DRG) neurons, as in the Trisomy 16 fetal mouse, an animal model of the human condition. Cultured trisomic DRG neurons from human and mouse fetuses present faster rates of depolarization and repolarization in the action potential compared to normal controls and a shorter spike duration. Also, Trisomy 16 brain and spinal cord tissue exhibit reduced acetylcholine secretion. Therefore, we decided to study Ca2+ currents in cultured DRG neurons from Trisomy 16 and age-matched control mice, using the whole-cell patch-clamp technique. Trisomic neurons exhibited a 62% reduction in Ca2+ current amplitude and reduced voltage dependence of current activation at -30 and -20 mV levels. Also, trisomic neurons showed slower activation kinetics for Ca2+ currents, with up to 80% increase in time constant values. Kinetics of the inactivation phase were similar in both conditions. The results indicate that murine Trisomy 16 alter Ca2+ currents, which may contribute to impaired cell function, including neurotransmitter release. These abnormalities also may alter neural development.
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Impaired cholinergic function in cell lines derived from the cerebral cortex of normal and Trisomy 16 mice.
The European journal of neuroscience, 2000Co-Authors: David D. Allen, Raúl Caviedes, Christian Arriagada, Stanley I. Rapoport, Ana María Cárdenas, José Martin, Pablo CaviedesAbstract:Murine Trisomy 16 is an animal model of human Down's syndrome. We have successfully established permanently growing cell lines from the cerebral cortex of normal and Trisomy 16 foetal mice using an original procedure. These lines, named CNh (derived from a normal animal) and CTb (derived from a trisomic foetus), express neuronal markers. Considering that Down's syndrome exhibits cholinergic deficits, we examined cholinergic function in these lines, using incorporation of [3H]-choline and fractional release studies. After 1, 3 and 5 min of [3H]-choline incubation, CTb cell uptake was lower by approximately 50% compared to controls. Hemicholinium-3 significantly reduced the incorporation of [3H]-choline in both CNh and CTb cells at high concentration (10 microM), suggesting high-affinity choline transport. However, CTb cells exhibited greater sensitivity to the blocker. For fractional release experiments, the cells were stimulated by K+ depolarization, glutamate or nicotine. When depolarized, CTb cells showed a 68% reduction in fractional release of [3H]-acetylcholine compared to CNh cell line, and a 45% reduction when stimulated by nicotine. Interestingly, glutamate induced similar levels of release in both cell types. The results indicate the existence of cholinergic dysfunction in CTb cells when compared to CNh, similar to that reported for primary cultures of Trisomy 16 brain tissue (Fiedler et al. 1994, Brain Res., 658, 27-32). Thus, the CTb cell line may serve as a model for the study of Down's syndrome pathophysiology.
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Calcium signals in cell lines derived from the cerebral cortex of normal and Trisomy 16 mice.
Neuroreport, 1999Co-Authors: Ana María Cárdenas, Raúl Caviedes, Stanley I. Rapoport, Maribel P. Rodríguez, Magdalena P. Cortés, Rocío Álvarez, Wei-zheng Wei, Takeshi Shimahara, Pablo CaviedesAbstract:WE established two immortalized cell lines from cerebral cortex of normal (CNh) and Trisomy 16 (CTb) mouse fetuses, an animal model of human Trisomy 21. Those cells loaded with the fluorescent Ca 2+ dyes, Indo-1 and Fluo-3, exhibited increments of intracellular Ca 2+ ([Ca 2+ ] i ) in response to external glutamate, NMDA, AMPA and kainate. CTb cells exhibited higher basal Ca 2+ concentrations and had higher amplitude and slower time-dependent kinetics in the decay than CNh cells, suggesting an impaired Ca 2+ buffering capacity in the Trisomy 16-derived cell line. Nicotine also induced increments of [Ca 2+ ] i . The CTb cell line could represent a model for studying cellular alterations related to Down syndrome.
Zygmunt Galdzicki - One of the best experts on this subject based on the ideXlab platform.
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abnormal synaptic plasticity in the ts1cje segmental Trisomy 16 mouse model of down syndrome
Neuropharmacology, 2005Co-Authors: Richard J Siarey, Charles J. Epstein, Angela J Villar, Zygmunt GaldzickiAbstract:Abstract Due to the homology between human chromosome 21 and mouse chromosome 16, Trisomy 16 mice are considered animal models of Down syndrome (DS). Abnormal hippocampal synaptic plasticity and behavior have been reported in the segmental Trisomy 16 Ts65Dn mouse. In the Ts1Cje DS mouse model, which has a shorter triplicated chromosomal segment than Ts65Dn, more subtle hippocampal behavioral deficits have been reported. In this study, we investigated CA1 hippocampal synaptic plasticity, long-term potentiation (LTP) and depression (LTD) in the Ts1Cje mouse. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 area of in vitro hippocampal slices from the Ts1Cje mouse and diploid controls, LTP was induced by a single tetanizing train pulse (1 s) at 100 Hz and LTD by a 900-pulse train at 1 Hz. We report for the first time that compared to diploid controls, the hippocampus from the Ts1Cje mouse had a smaller LTP and an increased LTD. The changes are less dramatic than had been reported previously for the Ts65Dn mouse. Furthermore, in the Ts1Cje mouse trains of pulses at both 20 Hz and 100 Hz produced a decrease in the evoked fEPSPs over the length of the train in comparison to diploid fEPSPs. These findings suggest that genes from Ts1Cje chromosome, including GIRK2 potassium channel, contribute to abnormal short- and long-term plasticity.
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in cortical cultures of Trisomy 16 mouse brain the upregulated metallothionein i ii fails to respond to h2o2 exposure or glutamate receptor stimulation
Brain Research, 1998Co-Authors: Marzia Scortegagna, Stanley I. Rapoport, Zygmunt Galdzicki, Ingeborg HanbauerAbstract:Abstract To assess whether a defective oxidative defense may contribute to Down's syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in primary cultures of cerebral cortex from fetal Trisomy 16 mice and their euploid littermates. Western blot analysis showed that MT-I/II was upregulated and the protein carbonyl content was higher in Trisomy 16 compared with euploid cultures. Addition of N-acetyl- l -cysteine to the culture medium reduced the increment of MT-I/II in Trisomy 16 cortical cells. In euploid, but not trisomic cortical cultures, kainic acid, trans-(±)-ACPD, or H2O2 exposure elicited a dose-dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II immunoblot densities were not increased beyond their elevated basal levels. In contrast, 25 μM Pb induced MT-I/II, to a similar extent, in cortical cultures from euploid and Trisomy 16 mice. This suggests that the antioxidant—but not the metal—response element of the MT-I/II promoter was altered by increased oxidative stress. Our data suggest that, in the Trisomy 16 mouse, the effects of increased production of reactive oxygen species, due to the increased SOD-1, GluR5, or amyloid precursor protein gene dosage, is exacerbated by an insufficient or missing antioxidant response.
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Evidence of increased oxidative stress in hippocampal primary cultures of Trisomy 16 mouse. Studies on metallothionein-I/II.
Restorative neurology and neuroscience, 1998Co-Authors: Ingeborg Hanbauer, Zygmunt Galdzicki, Stanley I. Rapoport, Marzia ScortegagnaAbstract:In the Trisomy 16 mouse the increased gene dosage of SOD-1 increases H 2 O 2 production that results in increased oxidative stress. We report here that in hippocampal primary cultures, metallothionein (MT)-I/II immunoreactivity was present mainly in glial fibrillary acidic protein-immunolabeled cells. Western blot analysis showed a two-fold higher level of MT-I/II in Trisomy 16 mice then in euploid littermates. In contrast, the immunoreactivity of glutamine synthetase, another glia-expressed protein, was similar in hippocampal cultures of Trisomy 16 mouse and euploid littermates. Oxyblot analysis of hippocampal cultures showed that the carbonyl content in several protein bands was higher in Trisomy 16 mice than in euploid littermates giving evidence for increased oxidative stress in Trisomy 16 mouse cultures. To evaluate the responsiveness of MT-I/II to agents that increase the level of reactive oxygen species in cells we measured the effect of H 2 O 2 , kainic acid, (±)ACPD, and β-amyloid peptide 1-42. Westem blot analysis documented that in hippocampal cultures of euploid littermates MT-I/II was maximally increased by 50 μM H 2 O 2 , 100 μM kainic acid, 10 μM (±)ACPD, or 1.0 mM β-amyloid peptide 1-42, whereas in those of Trisomy 16 mice no further increase above the elevated level was observed. Our data suggest that in the Trisomy 16 mouse the production of reactive oxygen species may have shifted the intracellular redox environment that could have altered the susceptibility of MT-I/II transcription. The possibility that transcription factors whose activation may be essential to initiate MT-I/II transcription get oxidized has yet to be examined.
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Decreased sensitivity to nerve growth factor of dorsal root ganglion neurons cultured from mouse Trisomy 16, a model of Down's syndrome.
Brain Research, 1995Co-Authors: Rosalyn Pearce, Zygmunt Galdzicki, Stanley I. RapoportAbstract:The effect of NGF was studied on the adhesion of mouse dorsal root ganglion (DRG) neurons to a laminin-coated surface and on their subsequent survival in primary culture. DRG neurons were obtained both from normal diploid mice and Trisomy 16 mice. The latter are considered a model of human Trisomy 21, Down's syndrome. Whereas both diploid and Trisomy DRG neurons depended on NGF for adhesion, the sensitivity of Trisomy 16 neurons to NGF was significantly reduced (P < 0.05). This suggests that excess expression of genes on mouse chromosome 16 alters NGF-regulated adhesion to laminin. Survival of neurons that had attached to laminin in culture did not appear dependent on NGF for either diploid or Trisomy 16 neurons.
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Cultured hippocampal neurons from Trisomy 16 mouse, a model for Down's syndrome, have an abnormal action potential due to a reduced inward sodium current.
Brain Research, 1993Co-Authors: Zygmunt Galdzicki, E.j. Coan, S. I. RapoportAbstract:Abstract Mouse Trisomy 16 is an animal model for Down's syndrome (human Trisomy 21). The whole-cell patch-clamp technique was used to compare passive and active electrical properties of Trisomy 16 and diploid mouse 16 fetal hippocampal neurons maintained in culture for 2–5 weeks. There was no significant difference in any mean passive property, including resting potential, membrane resistance, capacitance and time constant. However, in trisomic neurons, the action potential had a 20% significantly slower rising phase and a 20% significantly smaller inward sodium current and inward sodium conductance than did control neurons. The outward conductance was not altered. The ratio of maximum inward conductance to maximum outward conductance was 30% less in the Trisomy 16 cells. These results indicate that Trisomy 16 hippocampal neurons have abnormal active electrical properties, most likely reflecting reduced sodium channel membrane density. Such subtle differences may influence elaboration of the hippocampus during development.
T A Donlon - One of the best experts on this subject based on the ideXlab platform.
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Non-mosaic Trisomy 16 in a third-trimester fetus.
Obstetrics and gynecology, 1996Co-Authors: M K Yancey, E L Hardin, C Pacheco, C D Kuslich, T A DonlonAbstract:Trisomy 16 in the most common Trisomy first-trimester spontaneous abortions, suggesting a high rate of non-disjunction of this chromosome. Deoxyribonucleic acid studies in aborted conceptuses with Trisomy 16 have demonstrated a maternal origin in all cases. There have been cases of confined placental mosaicism, fetal mosaicism, and partial Trisomy involving chromosome 16 reported in term fetuses. However, to our knowledge, there have been no previous reports of a near-term fetus with full Trisomy 16 since the advent of modern chromosomal banding techniques. A 25-year-old Filipino woman underwent obstetric sonographic evaluation at 32 weeks' gestation; results were remarkable for oligohydramnios, severe growth restriction, and multiple dysmorphic features. Percutaneous umbilical blood sampling was performed for rapid karyotyping, viral serology, and blood profiles. The fetal karyotype was 47, XY+16; the remainder of the laboratory analysis was unremarkable. The patient went into spontaneous labor at 35 weeks' gestation and delivered a stillborn female fetus (birth weight 783 g). Chromosomes from skin, brain, and chorionic villi were examined and all demonstrated Trisomy 16 (47, XX,+16). Deoxyribonucleic acid primers for known polymorphic regions of chromosome 16 were used and determined the origin of the extra chromosome to be non-disjunction during paternal meiosis. Previously, full Trisomy 16 has been thought to be incompatible with fetal survival past the early second trimester. This case also contrasts with previously reported experience with Trisomy 16 in that parental origin studies determined that the extra chromosome 16 originated from the father, suggesting that paternal derivation of the additional chromosome may play a role in the ultimate phenotypic expression.
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Non-mosaic Trisomy 16 in a third-trimester fetus.
Obstetrics & Gynecology, 1996Co-Authors: M K Yancey, Pacheco C, T A DonlonAbstract:Background: Trisomy 16 is the most common Trisomy in first-trimester spontaneous abortions, suggesting a high rate of non-disjunction of this chromosome. Deoxyribonucleic acid studies in aborted conceptuses with Trisomy 16 have demonstrated a maternal origin in all cases. There have been cases of confined placental mosaicism, fetal mosaicism, and partial Trisomy involving chromosome 16 reported in term fetuses. However, to our knowledge, there have been no previous reports of a near-term fetus with full Trisomy 16 since the advent of modern chromosomal banding techniques. Case: A 25-year-old Filipino woman underwent obstetric sonographic evaluation at 32 weeks' gestation; results were remarkable for oligohydramnios, severe growth restriction, and multiple dysmorphic features. Percutaneous umbilical blood sampling was performed for rapid karyotyping, viral serology, and blood profiles. The fetal karyotype was 47,XX,+16; the remainder of the laboratory analysis was unremarkable. The patient went into spontaneous labor at 35 weeks' gestation and delivered a stillborn female fetus (birth weight 783 g). Chromosomes from skin, brain, and chorionic villi were examined and all demonstrated Trisomy 16 (47,XX,+16). Deoxyribonucleic acid primers for known polymorphic regions of chromosome 16 were used and determined the origin of the extra chromosome to be non-disjunction during paternal meiosis. Conclusion: Previously, full Trisomy 16 has been thought to be incompatible with fetal survival past the early second trimester. This case also contrasts with previously reported experience with Trisomy 16 in that parental origin studies determined that the extra chromosome 16 originated from the father, suggesting that paternal derivation of the additional chromosome may play a role in the ultimate phenotypic expression.
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Non-mosaic Trisomy 16 in a near-term child
American Journal of Human Genetics, 1994Co-Authors: T A Donlon, C D Kuslich, J.e. MurrayAbstract:Trisomy 16 is the most common Trisomy in first trimester spontaneous abortions, suggesting a high rate of non-disjunction. While cases of confined placental mosaicism and fetal mosaicism or partial Trisomy of chromosome 16 have been reported in term fetuses, there have been no previous reports of a near-term fetus with full Trisomy 16, indicating a high rate of selection against such cases. Our patient is a 25 year old Filipino female who underwent obstetrical sonographic evaluation at 32 weeks gestation due to suspicion of intrauterine growth retardation. Evaluation was remarkable for severe growth restriction and multiple dysmorphic features. The fetal karyotype was 47,XX,+16 (20 cells in blood, 30 cells from amniocytes); however, the remainder of the laboratory analysis was unremarkable. The patient went into spontaneous labor at 35 weeks gestation and had noted fetal movement prior to admission, but subsequently delivered a stillborn female fetus with a birthweight of 983 grams. Chromosomes from skin and brain fibroblasts and chorionic villus were examined and all (30 cells each) demonstrated Trisomy 16. Fetal autopsy confirmed the presence of multiple major structural defects including facial dismorphism, webbing of the neck and axilla, pulmonary hypoplasia, cardiosplenic syndrome, congenital diaphragmatic hernia, and agenesis of themore » corpus callosum. While full Trisomy 16 has previously been thought to be incompatible with fetal survival past the early second trimester, this case demonstrates this premise to be invalid. Previous studies by other laboratories have shown the extra chromosome 16 in aborted cases to be of maternal origin, consistent with a higher rate of maternal vs. paternal non-disjunction. The parental origin results of the present case will be presented.« less
Thomas Eggermann - One of the best experts on this subject based on the ideXlab platform.
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maternal uniparental disomy of chromosome 16 upd 16 mat clinical features are rather caused by hidden Trisomy 16 mosaicism than by upd 16 mat itself
Clinical Genetics, 2017Co-Authors: R Scheuvens, Matthias Begemann, Lukas Soellner, D Meschede, Gisela Raabemeyer, Miriam Elbracht, Regine Schubert, Thomas EggermannAbstract:Maternal uniparental disomy of chromosome 16 [upd(16)mat] as the result of Trisomy 16 is one of the most frequently reported uniparental disomies in humans, but a consistent phenotype is not obvious. Particularly, it is difficult to discriminate between features resulting from upd(16)mat and mosaic Trisomy 16. By evaluating literature data (n = 74) and three own cases we aimed to determine whether the clinical features are due to upd(16)mat or to Trisomy 16 mosaicism. While in single cases the clinical symptoms were caused by homozygosity of autosomal recessive mutations on chromosome 16, it turned out that clinical features in upd(16)mat are caused by (hidden) Trisomy 16 mosaicism and a specific chromosome 16-associated imprinting disorder does not exist. In Trisomy 16/upd(16)mat pregnancies, the management should be based on the ultrasound results and on the clinical course of the pregnancy. In fact, mosaic Trisomy 16 pregnancies require a close monitoring because of the higher risk for hypertensive disorders. Postnatal testing for upd(16)mat should be considered in case of homozygosity for an autosomal-recessive mutation, in individuals carrying chromosome 16 aberrations and in phenotypes comprising features of the Trisomy 16/upd(16)mat spectrum. Finally, upd(16)mat probably represents a bioindicator for a hidden Trisomy 16 mosaicism.
