Spolupracovali sme na publikáciach
2024
9.
Gazdarica, J.; Forgacova, N.; Sladecek, T.; Kucharik, M.; Budis, J.; Hyblova, M.; Sekelska, M.; Gnip, A.; Minarik, G.; Szemes, T.
Insights into non-informative results from non-invasive prenatal screening through gestational age, maternal BMI, and age analyses Journal Article
V: PLoS ONE, 19 (3 March), 2024, ISSN: 19326203.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Cell-free nucleic acids, Prenatal diagnosis
@article{Gazdarica2024,
title = {Insights into non-informative results from non-invasive prenatal screening through gestational age, maternal BMI, and age analyses},
author = {J. Gazdarica and N. Forgacova and T. Sladecek and M. Kucharik and J. Budis and M. Hyblova and M. Sekelska and A. Gnip and G. Minarik and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85187162464&doi=10.1371%2fjournal.pone.0280858&partnerID=40&md5=c7288799cea18fb3514ec062aa42a91f},
doi = {10.1371/journal.pone.0280858},
issn = {19326203},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {PLoS ONE},
volume = {19},
number = {3 March},
publisher = {Public Library of Science},
abstract = {The discovery of cell-free fetal DNA fragments in the maternal plasma initiated a novel testing method in prenatal care, called non-invasive prenatal screening (NIPS). One of the limitations of NIPS is the necessity for a sufficient proportion of fetal fragments in the analyzed circulating DNA mixture (fetal fraction), otherwise, the sample is uninterpretable. We present the effect of gestational age, maternal body mass index (BMI), and maternal age on the fetal fraction (FF) of the sample. We retrospectively analyzed data from 5543 pregnant women with a single male fetus who underwent NIPS from which 189 samples received a repeat testing due to an insufficient FF. We showed the relationship between the failure rate of the samples after the repeated analysis, the FF, and the gestational age at the first sampling. Next, we found that different maternal BMI categories affect the FF and thus the chance of an informative redraw. A better understanding of the factors affecting the FF will reduce the number of non-informative calls from repeated analyzes. In this study, we provide helpful information to clinicians on how to approach non-informative analyses. © 2024 Gazdarica et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},
keywords = {Aneuploidy, Cell-free nucleic acids, Prenatal diagnosis},
pubstate = {published},
tppubtype = {article}
}
The discovery of cell-free fetal DNA fragments in the maternal plasma initiated a novel testing method in prenatal care, called non-invasive prenatal screening (NIPS). One of the limitations of NIPS is the necessity for a sufficient proportion of fetal fragments in the analyzed circulating DNA mixture (fetal fraction), otherwise, the sample is uninterpretable. We present the effect of gestational age, maternal body mass index (BMI), and maternal age on the fetal fraction (FF) of the sample. We retrospectively analyzed data from 5543 pregnant women with a single male fetus who underwent NIPS from which 189 samples received a repeat testing due to an insufficient FF. We showed the relationship between the failure rate of the samples after the repeated analysis, the FF, and the gestational age at the first sampling. Next, we found that different maternal BMI categories affect the FF and thus the chance of an informative redraw. A better understanding of the factors affecting the FF will reduce the number of non-informative calls from repeated analyzes. In this study, we provide helpful information to clinicians on how to approach non-informative analyses. © 2024 Gazdarica et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
2020
8.
Soltysova, A; Sedlackova, T; Dvorska, D; Jasek, K; Baradaran, P C; Kajabova, V H; Demkova, L; Buocikova, V; Kurucova, T; Lyskova, D; Furdova, A; Minarik, G; Babal, P; Dankova, Z; Smolkova, B
Monosomy 3 influences epithelial-mesenchymal transition gene expression in uveal melanoma patients; consequences for liquid biopsy Journal Article
V: International Journal of Molecular Sciences, 21 (24), pp. 1-24, 2020, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Body fluids, Circulating tumor cells, Liquid biopsy, Oncology
@article{Soltysova20201,
title = {Monosomy 3 influences epithelial-mesenchymal transition gene expression in uveal melanoma patients; consequences for liquid biopsy},
author = {A Soltysova and T Sedlackova and D Dvorska and K Jasek and P C Baradaran and V H Kajabova and L Demkova and V Buocikova and T Kurucova and D Lyskova and A Furdova and G Minarik and P Babal and Z Dankova and B Smolkova},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097833518&doi=10.3390%2fijms21249651&partnerID=40&md5=133b8d5d56ebac3bf7a09024f007273e},
doi = {10.3390/ijms21249651},
issn = {16616596},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {24},
pages = {1-24},
publisher = {MDPI AG},
abstract = {Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCβ4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Aneuploidy, Body fluids, Circulating tumor cells, Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCβ4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
2019
7.
Sekelska, M; Izsakova, A; Kubosova, K; Tilandyova, P; Csekes, E; Kuchova, Z; Hyblova, M; Harsanyova, M; Kucharik, M; Budis, J; Szemes, T; Minarik, G
Result of prospective validation of the trisomy Test® for the detection of chromosomal trisomies Journal Article
V: Diagnostics, 9 (4), 2019, ISSN: 20754418.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Fetal fraction, Non-invasive prenatal testing, Validation
@article{Sekelska2019,
title = {Result of prospective validation of the trisomy Test® for the detection of chromosomal trisomies},
author = {M Sekelska and A Izsakova and K Kubosova and P Tilandyova and E Csekes and Z Kuchova and M Hyblova and M Harsanyova and M Kucharik and J Budis and T Szemes and G Minarik},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076805864&doi=10.3390%2fdiagnostics9040138&partnerID=40&md5=ffdda3394730383358ea467fee4a90f8},
doi = {10.3390/diagnostics9040138},
issn = {20754418},
year = {2019},
date = {2019-01-01},
journal = {Diagnostics},
volume = {9},
number = {4},
publisher = {MDPI AG},
abstract = {Noninvasive prenatal testing (NIPT) is one of the most common prenatal screening tests used worldwide. Trisomy Test® belongs to NIPT tests based on low-coverage whole-genome sequencing. In our prospective study, 7279 samples of pregnant women collected during approximately two years were analyzed. In this cohort, 117 positive cases for trisomies 21, 18, and 13 were reported. An in-house designed bioinformatic pipeline and proprietary biostatistical approach was used for the detection of trisomies. The pooled sensitivity and specificity of our test reached 99.12% and 99.94%, respectively. The proportion of repeatedly uninformative results after repeated blood draws was 1.11%. Based on the presented results, we can confirm that the Trisomy Test® is fully comparable with other commercial NIPT tests available worldwide. © 2019 by the authors.},
keywords = {Aneuploidy, Fetal fraction, Non-invasive prenatal testing, Validation},
pubstate = {published},
tppubtype = {article}
}
Noninvasive prenatal testing (NIPT) is one of the most common prenatal screening tests used worldwide. Trisomy Test® belongs to NIPT tests based on low-coverage whole-genome sequencing. In our prospective study, 7279 samples of pregnant women collected during approximately two years were analyzed. In this cohort, 117 positive cases for trisomies 21, 18, and 13 were reported. An in-house designed bioinformatic pipeline and proprietary biostatistical approach was used for the detection of trisomies. The pooled sensitivity and specificity of our test reached 99.12% and 99.94%, respectively. The proportion of repeatedly uninformative results after repeated blood draws was 1.11%. Based on the presented results, we can confirm that the Trisomy Test® is fully comparable with other commercial NIPT tests available worldwide. © 2019 by the authors.
6.
Gazdarica, J; Hekel, R; Budis, J; Kucharik, M; Duris, F; Radvanszky, J; Turna, J; Szemes, T
Combination of fetal fraction estimators based on fragment lengths and fragment counts in non-invasive prenatal testing Journal Article
V: International Journal of Molecular Sciences, 20 (16), 2019, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Computational method, Fetal fraction, Non-invasive prenatal testing
@article{Gazdarica2019,
title = {Combination of fetal fraction estimators based on fragment lengths and fragment counts in non-invasive prenatal testing},
author = {J Gazdarica and R Hekel and J Budis and M Kucharik and F Duris and J Radvanszky and J Turna and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071515046&doi=10.3390%2fijms20163959&partnerID=40&md5=13c0a797eeb085dba097cea3d39680a9},
doi = {10.3390/ijms20163959},
issn = {16616596},
year = {2019},
date = {2019-01-01},
journal = {International Journal of Molecular Sciences},
volume = {20},
number = {16},
publisher = {MDPI AG},
abstract = {The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Aneuploidy, Computational method, Fetal fraction, Non-invasive prenatal testing},
pubstate = {published},
tppubtype = {article}
}
The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
5.
Gazdarica, J; Budis, J; Duris, F; Turna, J; Szemes, T
Adaptable model parameters in non-invasive prenatal testing lead to more stable predictions Journal Article
V: International Journal of Molecular Sciences, 20 (14), 2019, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Computational method, Non-invasive prenatal testing
@article{Gazdarica2019b,
title = {Adaptable model parameters in non-invasive prenatal testing lead to more stable predictions},
author = {J Gazdarica and J Budis and F Duris and J Turna and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070461646&doi=10.3390%2fijms20143414&partnerID=40&md5=055222c81da89a9a0300464ee09b9c1b},
doi = {10.3390/ijms20143414},
issn = {16616596},
year = {2019},
date = {2019-01-01},
journal = {International Journal of Molecular Sciences},
volume = {20},
number = {14},
publisher = {MDPI AG},
abstract = {Recent advances in massively parallel shotgun sequencing opened up new options for affordable non-invasive prenatal testing (NIPT) for fetus aneuploidy from DNA material extracted from maternal plasma. Tests typically compare chromosomal distributions of a tested sample with a control set of healthy samples with unaffected fetuses. Deviations above certain threshold levels are concluded as positive findings. The main problem with this approach is that the variance of the control set is dependent on the number of sequenced fragments. The higher the amount, the more precise the estimation of actual chromosomal proportions is. Testing a sample with a highly different number of sequenced reads as used in training may thus lead to over- or under-estimation of their variance, and so lead to false predictions. We propose the calculation of a variance for each tested sample adaptively, based on the actual number of its sequenced fragments. We demonstrate how it leads to more stable predictions, mainly in real-world diagnostics with the highly divergent inter-sample coverage. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Aneuploidy, Computational method, Non-invasive prenatal testing},
pubstate = {published},
tppubtype = {article}
}
Recent advances in massively parallel shotgun sequencing opened up new options for affordable non-invasive prenatal testing (NIPT) for fetus aneuploidy from DNA material extracted from maternal plasma. Tests typically compare chromosomal distributions of a tested sample with a control set of healthy samples with unaffected fetuses. Deviations above certain threshold levels are concluded as positive findings. The main problem with this approach is that the variance of the control set is dependent on the number of sequenced fragments. The higher the amount, the more precise the estimation of actual chromosomal proportions is. Testing a sample with a highly different number of sequenced reads as used in training may thus lead to over- or under-estimation of their variance, and so lead to false predictions. We propose the calculation of a variance for each tested sample adaptively, based on the actual number of its sequenced fragments. We demonstrate how it leads to more stable predictions, mainly in real-world diagnostics with the highly divergent inter-sample coverage. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
4.
Budis, J; Gazdarica, J; Radvanszky, J; Szucs, G; Kucharik, M; Strieskova, L; Gazdaricova, I; Harsanyova, M; Duris, F; Minarik, G; Sekelska, M; Nagy, B; Turna, J; Szemes, T
Combining count- And length-based z-scores leads to improved predictions in non-invasive prenatal testing Journal Article
V: Bioinformatics, 35 (8), pp. 1284-1291, 2019, ISSN: 13674803.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Computational method, Fetal fraction, Non-invasive prenatal testing, Prenatal diagnosis
@article{Budis20191284,
title = {Combining count- And length-based z-scores leads to improved predictions in non-invasive prenatal testing},
author = {J Budis and J Gazdarica and J Radvanszky and G Szucs and M Kucharik and L Strieskova and I Gazdaricova and M Harsanyova and F Duris and G Minarik and M Sekelska and B Nagy and J Turna and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85067353429&doi=10.1093%2fbioinformatics%2fbty806&partnerID=40&md5=c63c304db3eb59cb922d0ca8e3a9e76a},
doi = {10.1093/bioinformatics/bty806},
issn = {13674803},
year = {2019},
date = {2019-01-01},
journal = {Bioinformatics},
volume = {35},
number = {8},
pages = {1284-1291},
publisher = {Oxford University Press},
abstract = {Motivation: Non-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test. Results: We propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls. Availability and implementation: The open-source code of the proposed methods, together with test data, is freely available for non-commercial users at github web page https://github.com/jbudis/lambda. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.},
keywords = {Aneuploidy, Computational method, Fetal fraction, Non-invasive prenatal testing, Prenatal diagnosis},
pubstate = {published},
tppubtype = {article}
}
Motivation: Non-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test. Results: We propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls. Availability and implementation: The open-source code of the proposed methods, together with test data, is freely available for non-commercial users at github web page https://github.com/jbudis/lambda. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.
2018
3.
Duris, F; Gazdarica, J; Gazdaricova, I; Strieskova, L; Budis, J; Turna, J; Szemes, T
Mean and variance of ratios of proportions from categories of a multinomial distribution Journal Article
V: Journal of Statistical Distributions and Applications, 5 (1), 2018, ISSN: 21955832.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Computational method, Non-invasive prenatal testing
@article{Duris2018,
title = {Mean and variance of ratios of proportions from categories of a multinomial distribution},
author = {F Duris and J Gazdarica and I Gazdaricova and L Strieskova and J Budis and J Turna and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062689021&doi=10.1186%2fs40488-018-0083-x&partnerID=40&md5=d293ac604976bfd7c1b99a1bb71fd1f2},
doi = {10.1186/s40488-018-0083-x},
issn = {21955832},
year = {2018},
date = {2018-01-01},
journal = {Journal of Statistical Distributions and Applications},
volume = {5},
number = {1},
publisher = {Springer},
abstract = {Ratio distribution is a probability distribution representing the ratio of two random variables, each usually having a known distribution. Currently, there are results when the random variables in the ratio follow (not necessarily the same) Gaussian, Cauchy, binomial or uniform distributions. In this paper we consider a case, where the random variables in the ratio are joint binomial components of a multinomial distribution. We derived formulae for mean and variance of this ratio distribution using a simple Taylor-series approach and also a more complex approach which uses a slight modification of the original ratio. We showed that the more complex approach yields better results with simulated data. The presented results can be directly applied in the computation of confidence intervals for ratios of multinomial proportions. AMS Subject Classification: 62E20. © 2018, The Author(s).},
keywords = {Aneuploidy, Computational method, Non-invasive prenatal testing},
pubstate = {published},
tppubtype = {article}
}
Ratio distribution is a probability distribution representing the ratio of two random variables, each usually having a known distribution. Currently, there are results when the random variables in the ratio follow (not necessarily the same) Gaussian, Cauchy, binomial or uniform distributions. In this paper we consider a case, where the random variables in the ratio are joint binomial components of a multinomial distribution. We derived formulae for mean and variance of this ratio distribution using a simple Taylor-series approach and also a more complex approach which uses a slight modification of the original ratio. We showed that the more complex approach yields better results with simulated data. The presented results can be directly applied in the computation of confidence intervals for ratios of multinomial proportions. AMS Subject Classification: 62E20. © 2018, The Author(s).
2017
2.
Cierna, Z; Janega, P; Grochal, F; Ferianec, V; Braxatorisova, T; Strieskova, L; Malova, J; Jungova, P; Szemes, T
The first reported case of meckel-gruber syndrome associated with abnormal karyotype mosaic trisomy 17 Journal Article
V: Pediatric and Developmental Pathology, 20 (5), pp. 449-454, 2017, ISSN: 10935266.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Case study, Genetic testing
@article{Cierna2017449,
title = {The first reported case of meckel-gruber syndrome associated with abnormal karyotype mosaic trisomy 17},
author = {Z Cierna and P Janega and F Grochal and V Ferianec and T Braxatorisova and L Strieskova and J Malova and P Jungova and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032002622&doi=10.1177%2f1093526616689184&partnerID=40&md5=8458f3e2bde61a3a4f9694e41e605a73},
doi = {10.1177/1093526616689184},
issn = {10935266},
year = {2017},
date = {2017-01-01},
journal = {Pediatric and Developmental Pathology},
volume = {20},
number = {5},
pages = {449-454},
publisher = {SAGE Publications Ltd},
abstract = {Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive disorder with typical anomalies including encephalocele, multicystic renal dysplasia, congenital liver fibrosis, and polydactyly. MKS is caused by mutations of genes localized on different chromosomes. Karyotypes of published Meckel-Gruber syndrome cases are without any aberrations. We present a male fetus with meningoencephalocele, multicystic renal dysplasia, congenital liver fibrosis, and other anomalies. Standard cytogenetic examination of cultured fetal skin and muscle fibroblasts showed mosaic trisomy 17. Homozygous deletion in CC2D2A gene was found by Sanger sequencing. This is to our knowledge the first case of genetically confirmed Meckel- Gruber syndrome with incidental cofinding of mosaic trisomy 17. Abnormal karyotype does not exclude diagnosis of MKS with risk of recurrence 25% in next pregnancy. In the case of anomalies typical for Meckel-Gruber syndrome, genetic analysis is indicated. © 2017, Society for Pediatric Pathology.},
keywords = {Aneuploidy, Case study, Genetic testing},
pubstate = {published},
tppubtype = {article}
}
Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive disorder with typical anomalies including encephalocele, multicystic renal dysplasia, congenital liver fibrosis, and polydactyly. MKS is caused by mutations of genes localized on different chromosomes. Karyotypes of published Meckel-Gruber syndrome cases are without any aberrations. We present a male fetus with meningoencephalocele, multicystic renal dysplasia, congenital liver fibrosis, and other anomalies. Standard cytogenetic examination of cultured fetal skin and muscle fibroblasts showed mosaic trisomy 17. Homozygous deletion in CC2D2A gene was found by Sanger sequencing. This is to our knowledge the first case of genetically confirmed Meckel- Gruber syndrome with incidental cofinding of mosaic trisomy 17. Abnormal karyotype does not exclude diagnosis of MKS with risk of recurrence 25% in next pregnancy. In the case of anomalies typical for Meckel-Gruber syndrome, genetic analysis is indicated. © 2017, Society for Pediatric Pathology.
2015
1.
Minarik, G; Repiska, G; Hyblova, M; Nagyova, E; Soltys, K; Budis, J; Duris, F; Sysak, R; Bujalkova, M G; Vlkova-Izrael, B; Biro, O; Nagy, B; Szemes, T
V: PLoS ONE, 10 (12), 2015, ISSN: 19326203.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Non-invasive prenatal testing, Size selection, Validation
@article{Minarik2015,
title = {Utilization of benchtop next generation sequencing platforms ion torrent PGM and miseq in noninvasive prenatal testing for chromosome 21 trisomy and testing of impact of in silico and physical size selection on its analytical performance},
author = {G Minarik and G Repiska and M Hyblova and E Nagyova and K Soltys and J Budis and F Duris and R Sysak and M G Bujalkova and B Vlkova-Izrael and O Biro and B Nagy and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956618019&doi=10.1371%2fjournal.pone.0144811&partnerID=40&md5=ba19c1dabbdb0f2c2d3718fd27e8fc9c},
doi = {10.1371/journal.pone.0144811},
issn = {19326203},
year = {2015},
date = {2015-01-01},
journal = {PLoS ONE},
volume = {10},
number = {12},
publisher = {Public Library of Science},
abstract = {Objectives The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. Methods Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied. Results Using a z score value of 3 as the cut-off, 98.11% - 100% (104-106/106) specificity and 100% (24/24) sensitivity and 99.06% - 100% (105-106/106) specificity and 100% (24/24) sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantlyâ€"p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively. Conclusions Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on highto- ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide. © 2015 Minarik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},
keywords = {Aneuploidy, Non-invasive prenatal testing, Size selection, Validation},
pubstate = {published},
tppubtype = {article}
}
Objectives The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. Methods Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied. Results Using a z score value of 3 as the cut-off, 98.11% - 100% (104-106/106) specificity and 100% (24/24) sensitivity and 99.06% - 100% (105-106/106) specificity and 100% (24/24) sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantlyâ€"p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively. Conclusions Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on highto- ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide. © 2015 Minarik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.