Full Monosomy 21, Prenatally Diagnosed by Fluorescentin Situ Hybridization

Joosten, Anne M. S.; Vos, Sandra De; Opstal, Diane Van; Brandenburg, Helen; Gaillard, J. L. J.; Vermeij‐Keers, Christl

doi:10.1002/(sici)1097-0223(199703)17:3<271::aid-pd51>3.0.co;2-p

Cited by 25 publications

(19 citation statements)

References 19 publications

(21 reference statements)

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“…In two cases, the retained chromosome 21 was determined to be of paternal origin implicating a maternal meiosis I nondisjunction event. 38,39 The frequency of monosomy 21 vs. other autosomal monosomies in our series suggests a greater survival advantage for this autosomal monosomy.…”

Section: Chromosome Versus Fish Analyses For Abnormality Detectionmentioning

confidence: 59%

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Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: A retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization

Shearer

Thorland

Carlson

et al. 2011

Genetics in Medicine

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Introduction:The use of chromosome analysis on products of conception from spontaneous abortions is recommended to identify a genetic etiology. However, 20% of products of conception cultures are unsuccessful due to microbial contamination or lack of viable dividing cells. Our laboratory implemented a reflex fluorescent in situ hybridization (FISH) assay to detect numeric chromosome abnormalities for unsuccessful cultures. Materials and Methods: All products of conception samples were simultaneously processed for both chromosome analysis and FISH analysis. If the chromosome analysis was unsuccessful, interphase FISH was performed for chromosomes 13,16,18,21,22, X, and Y. To assess the performance of the FISH assay, a 3-year retrospective comparative analysis of the FISH results versus chromosome results was performed. Results: Of 5555 total specimens, 4189 (75%) represented chorionic villi/fetal tissue and 1366 (25%) represented tissue of unidentified origin. Of the 1189 tissues of unidentified origin with chromosome or FISH results, 1096 (92%) were XX, indicating that the majority of these tissues are likely maternal in origin. Of the 3361 successful chromosome studies on the chorionic villi/fetal tissue specimens, 1734 (52%) samples had a chromosome abnormality. Of the 762 successful FISH studies on chorionic villi/fetal tissue specimens that were unsuccessful by chromosome studies, 181 (25%) had an abnormal result with the targeted FISH panel. Overall, the FISH panel detected approximately 70% of the chromosome abnormalities in products of conception detectable by karyotype. When the FISH panel results were combined with chromosome analysis for the 4189 chorionic villi/fetal tissue specimens, the overall abnormality rate is 47%. Conclusions: Our reflex FISH assay proved useful for the detection of common chromosome aneuploidies in products of conception samples that failed conventional chromosome analysis. Because of its limited view of the genome, cautious interpretation of FISH results is required for all samples, in particular, trisomy of an acrocentric chromosome, which may represent a Robertsonian translocation. An algorithmic approach to the genetic evaluation of products of conception specimens, with the potential for initial evaluation by a FISH panel, may be warranted. Genet Med 2011:13(6):545-552.

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Section: Chromosome Versus Fish Analyses For Abnormality Detectionmentioning

confidence: 59%

“…Our data are similar to that of Menasha et al, 30 where 11 of 13 autosomal monosomies involved chromosome 21. Monosomy 21 has also been described prenatally 38,39 and in liveborns. 40 -45 The majority of these cases did not have molecular confirmation of true monosomy 21.…”

Section: Chromosome Versus Fish Analyses For Abnormality Detectionmentioning

confidence: 97%

Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: A retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization

Shearer

Thorland

Carlson

et al. 2011

Genetics in Medicine

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“…As predicted, we obtained Dp(16)1Yey/Df(16)2Yey progeny from this cross, providing evidence that the Tiam1-Kcnj6 region contains a gene(s) associated with haploinsufficient lethality. This gene(s) may underlie the embryonic lethality associated with human monosomy 21 (Chang et al 2001; Joosten et al 1997). The duplication was designated as Dup(16Tiam1-Kcnj6)Yey , abbreviated as Dp(16)2Yey or Ts4Yey.…”

Section: Resultsmentioning

confidence: 99%

Genetic analysis of Down syndrome-associated heart defects in mice

Liu

Morishima

et al. 2011

Hum Genet

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Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Has21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e., Dp(16)1Yey, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between Tiam1 and Kcnj6 using chromosome engineering, Dp(Tiam1-Kcnj6)Yey/+ and Df(Tiam1-Kcnj6)Yey/+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that Dp(Tiam1-Kcnj6)Yey/+, but not Dp(16)1Yey/Df(Tiam1-Kcnj6)Yey, resulted in heart defects, indicating that triplication of the Tiam1-Knj6 region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(Tiam1-Kcnj6)Yey/+ embryos confirmed elevated expression levels for the genes located in the Tiam-Kcnj6 region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype.

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“…As predicted, we obtained Dp(16)1Yey/Df(16)4Yey progeny from this cross, providing evidence that the Ifnar1-Kcnj6 region contains a gene(s) associated with haploinsufficient lethality. This gene(s) may underlie the embryonic lethality associated with human monosomy 21 (Chang et al 2001; Joosten et al 1997). The duplication was designated as Dup(16Ifnar1-Kcnj6)Yey , abbreviated as Dp(16)4Yey or Ts6Yey.…”

Section: Resultsmentioning

confidence: 99%

Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice

et al. 2013

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Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1Mb Tiam1-Il10rb and 3.7Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

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Full Monosomy 21, Prenatally Diagnosed by Fluorescentin Situ Hybridization

Cited by 25 publications

References 19 publications

Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: A retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization

Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: A retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization

Genetic analysis of Down syndrome-associated heart defects in mice

Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice

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