Spolupracovali sme na publikáciach
2025
9.
Horti-Oravecz, Klaudia; Bozsik, Anikó; Pócza, Tímea; Vereczkey, Ildikó; Strausz, Tamás; Tóth, Erika; Sedlackova, Tatiana; Rusnakova, Diana; Szemes, Tomas; Likó, István; Oláh, Edit; Butz, Henriett; Patócs, Attila; Papp, János; Grolmusz, Vince Kornél
Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome Journal Article
V: npj Genomic Medicine, 10 (1), 2025, ISSN: 20567944.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Oncology
@article{Horti-Oravecz2025,
title = {Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome},
author = {Klaudia Horti-Oravecz and Anikó Bozsik and Tímea Pócza and Ildikó Vereczkey and Tamás Strausz and Erika Tóth and Tatiana Sedlackova and Diana Rusnakova and Tomas Szemes and István Likó and Edit Oláh and Henriett Butz and Attila Patócs and János Papp and Vince Kornél Grolmusz},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85218225344&doi=10.1038%2fs41525-025-00461-z&partnerID=40&md5=f46292994e758b7a6c8b581f44c1938a},
doi = {10.1038/s41525-025-00461-z},
issn = {20567944},
year = {2025},
date = {2025-01-01},
urldate = {2025-01-01},
journal = {npj Genomic Medicine},
volume = {10},
number = {1},
publisher = {Nature Research},
abstract = {Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its’ pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS. © The Author(s) 2025.},
keywords = {Genetic testing, Oncology},
pubstate = {published},
tppubtype = {article}
}
Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its’ pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS. © The Author(s) 2025.
2022
8.
Forgacova, N.; Gazdarica, J.; Budis, J.; Kucharik, M.; Sekelska, M.; Szemes, T.
V: Molecular and Cellular Probes, 66 , 2022, ISSN: 08908508.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Non-invasive prenatal testing, Prenatal diagnosis
@article{Forgacova2022,
title = {Non-intuitive trends of fetal fraction development related to gestational age and fetal gender, and their practical implications for non-invasive prenatal testing},
author = {N. Forgacova and J. Gazdarica and J. Budis and M. Kucharik and M. Sekelska and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141451340&doi=10.1016%2fj.mcp.2022.101870&partnerID=40&md5=5f0a0eeb4603486d4288fc56950e00fe},
doi = {10.1016/j.mcp.2022.101870},
issn = {08908508},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Molecular and Cellular Probes},
volume = {66},
publisher = {Academic Press},
abstract = {Discovery of fetal cell-free DNA fragments in maternal blood revolutionized prenatal diagnostics. Although non-invasive prenatal testing (NIPT) is already a matured screening test with high specificity and sensitivity, the accurate estimation of the proportion of fetal fragments, called fetal fraction, is crucial to avoid false-negative results. In this study, we collected 6999 samples from women undergoing NIPT testing with a single male fetus to demonstrate the influence of fetal fraction by the maternal and fetal characteristics. We show several fetal fraction discrepancies that contradict the generally presented conventional view. At first, the fetal fraction is not consistently rising with the maturity of the fetus due to a drop in 15 weeks of maturation. Secondly, the male samples have a lower fetal fraction than female fetuses, arguably due to the smaller gonosomal chromosomes. Finally, we discuss not only the possible reasons why this inconsistency exists but we also outline why these differences have not yet been identified and published. We demonstrate two non-intuitive trends to better comprehend the fetal fraction development and more precise selection of patients with sufficient fetal fraction for accurate testing. © 2022 The Authors},
keywords = {Genetic testing, Non-invasive prenatal testing, Prenatal diagnosis},
pubstate = {published},
tppubtype = {article}
}
Discovery of fetal cell-free DNA fragments in maternal blood revolutionized prenatal diagnostics. Although non-invasive prenatal testing (NIPT) is already a matured screening test with high specificity and sensitivity, the accurate estimation of the proportion of fetal fragments, called fetal fraction, is crucial to avoid false-negative results. In this study, we collected 6999 samples from women undergoing NIPT testing with a single male fetus to demonstrate the influence of fetal fraction by the maternal and fetal characteristics. We show several fetal fraction discrepancies that contradict the generally presented conventional view. At first, the fetal fraction is not consistently rising with the maturity of the fetus due to a drop in 15 weeks of maturation. Secondly, the male samples have a lower fetal fraction than female fetuses, arguably due to the smaller gonosomal chromosomes. Finally, we discuss not only the possible reasons why this inconsistency exists but we also outline why these differences have not yet been identified and published. We demonstrate two non-intuitive trends to better comprehend the fetal fraction development and more precise selection of patients with sufficient fetal fraction for accurate testing. © 2022 The Authors
2021
7.
Pecimonova, M; Radvanszky, J; Smolak, D; Budis, J; Lichvar, M; Kristinova, D; Rozova, I; Turna, J; Szemes, T
Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report Journal Article
V: Medicine, 100 (22), pp. e26136, 2021, ISSN: 15365964.
Abstrakt | Linky | BibTeX | Značky: Case study, Genetic testing, Single nucleotide variants, Variant interpretation
@article{Pecimonova2021e26136,
title = {Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report},
author = {M Pecimonova and J Radvanszky and D Smolak and J Budis and M Lichvar and D Kristinova and I Rozova and J Turna and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107796467&doi=10.1097%2fMD.0000000000026136&partnerID=40&md5=6d8eac607b0de5b1897c2cee34a64ec9},
doi = {10.1097/MD.0000000000026136},
issn = {15365964},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Medicine},
volume = {100},
number = {22},
pages = {e26136},
publisher = {NLM (Medline)},
abstract = {RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.},
keywords = {Case study, Genetic testing, Single nucleotide variants, Variant interpretation},
pubstate = {published},
tppubtype = {article}
}
RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
2019
6.
Kubiritova, Z; Gyuraszova, M; Nagyova, E; Hyblova, M; Harsanyova, M; Budis, J; Hekel, R; Gazdarica, J; Duris, F; Kadasi, L; Szemes, T; Radvanszky, J
On the critical evaluation and confirmation of germline sequence variants identified using massively parallel sequencing Journal Article
V: Journal of Biotechnology, 298 , pp. 64-75, 2019, ISSN: 01681656.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Single nucleotide variants, Validation, Variant calling
@article{Kubiritova201964,
title = {On the critical evaluation and confirmation of germline sequence variants identified using massively parallel sequencing},
author = {Z Kubiritova and M Gyuraszova and E Nagyova and M Hyblova and M Harsanyova and J Budis and R Hekel and J Gazdarica and F Duris and L Kadasi and T Szemes and J Radvanszky},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064435175&doi=10.1016%2fj.jbiotec.2019.04.013&partnerID=40&md5=175358cc48df08933da3da830780ad66},
doi = {10.1016/j.jbiotec.2019.04.013},
issn = {01681656},
year = {2019},
date = {2019-01-01},
journal = {Journal of Biotechnology},
volume = {298},
pages = {64-75},
publisher = {Elsevier B.V.},
abstract = {Although massively parallel sequencing (MPS) is becoming common practice in both research and routine clinical care, confirmation requirements of identified DNA variants using alternative methods are still topics of debate. When evaluating variants directly from MPS data, different read depth statistics, together with specialized genotype quality scores are, therefore, of high relevance. Here we report results of our validation study performed in two different ways: 1) confirmation of MPS identified variants using Sanger sequencing; and 2) simultaneous Sanger and MPS analysis of exons of selected genes. Detailed examination of false-positive and false-negative findings revealed typical error sources connected to low read depth/coverage, incomplete reference genome, indel realignment problems, as well as microsatellite associated amplification errors leading to base miss-calling. However, all these error types were identifiable with thorough manual revision of aligned reads according to specific patterns of distributions of variants and their corresponding reads. Moreover, our results point to dependence of both basic quantitative metrics (such as total read counts, alternative allele read counts and allelic balance) together with specific genotype quality scores on the used bioinformatics pipeline, stressing thus the need for establishing of specific thresholds for these metrics in each laboratory and for each involved pipeline independently. © 2019 Elsevier B.V.},
keywords = {Genetic testing, Single nucleotide variants, Validation, Variant calling},
pubstate = {published},
tppubtype = {article}
}
Although massively parallel sequencing (MPS) is becoming common practice in both research and routine clinical care, confirmation requirements of identified DNA variants using alternative methods are still topics of debate. When evaluating variants directly from MPS data, different read depth statistics, together with specialized genotype quality scores are, therefore, of high relevance. Here we report results of our validation study performed in two different ways: 1) confirmation of MPS identified variants using Sanger sequencing; and 2) simultaneous Sanger and MPS analysis of exons of selected genes. Detailed examination of false-positive and false-negative findings revealed typical error sources connected to low read depth/coverage, incomplete reference genome, indel realignment problems, as well as microsatellite associated amplification errors leading to base miss-calling. However, all these error types were identifiable with thorough manual revision of aligned reads according to specific patterns of distributions of variants and their corresponding reads. Moreover, our results point to dependence of both basic quantitative metrics (such as total read counts, alternative allele read counts and allelic balance) together with specific genotype quality scores on the used bioinformatics pipeline, stressing thus the need for establishing of specific thresholds for these metrics in each laboratory and for each involved pipeline independently. © 2019 Elsevier B.V.
5.
Budiš, J; Kucharík, M; Duriš, F; Gazdarica, J; Zrubcová, M; Ficek, A; Szemes, T; Brejová, B; Radvanszky, J
Dante: Genotyping of known complex and expanded short tandem repeats Journal Article
V: Bioinformatics, 35 (8), pp. 1310-1317, 2019, ISSN: 13674803.
Abstrakt | Linky | BibTeX | Značky: Computational method, Genetic testing, Short tandem repeats, Variant calling
@article{Budiš20191310,
title = {Dante: Genotyping of known complex and expanded short tandem repeats},
author = {J Budiš and M Kucharík and F Duriš and J Gazdarica and M Zrubcová and A Ficek and T Szemes and B Brejová and J Radvanszky},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064435619&doi=10.1093%2fbioinformatics%2fbty791&partnerID=40&md5=7e873f64aff7726aeb724a3a0c37237f},
doi = {10.1093/bioinformatics/bty791},
issn = {13674803},
year = {2019},
date = {2019-01-01},
journal = {Bioinformatics},
volume = {35},
number = {8},
pages = {1310-1317},
publisher = {Oxford University Press},
abstract = {Motivation: Short tandem repeats (STRs) are stretches of repetitive DNA in which short sequences, typically made of 2-6 nucleotides, are repeated several times. Since STRs have many important biological roles and also belong to the most polymorphic parts of the human genome, they became utilized in several molecular-genetic applications. Precise genotyping of STR alleles, therefore, was of high relevance during the last decades. Despite this, massively parallel sequencing (MPS) still lacks the analysis methods to fully utilize the information value of STRs in genome scale assays. Results: We propose an alignment-free algorithm, called Dante, for genotyping and characterization of STR alleles at user-specified known loci based on sequence reads originating from STR loci of interest. The method accounts for natural deviations from the expected sequence, such as variation in the repeat count, sequencing errors, ambiguous bases and complex loci containing several different motifs. In addition, we implemented a correction for copy number defects caused by the polymerase induced stutter effect as well as a prediction of STR expansions that, according to the conventional view, cannot be fully captured by inherently short MPS reads. We tested Dante on simulated datasets and on datasets obtained by targeted sequencing of protein coding parts of thousands of selected clinically relevant genes. In both these datasets, Dante outperformed HipSTR and GATK genotyping tools. Furthermore, Dante was able to predict allele expansions in all tested clinical cases. Availability and implementation: Dante is open source software, freely available for download at https://github.com/jbudis/dante. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.},
keywords = {Computational method, Genetic testing, Short tandem repeats, Variant calling},
pubstate = {published},
tppubtype = {article}
}
Motivation: Short tandem repeats (STRs) are stretches of repetitive DNA in which short sequences, typically made of 2-6 nucleotides, are repeated several times. Since STRs have many important biological roles and also belong to the most polymorphic parts of the human genome, they became utilized in several molecular-genetic applications. Precise genotyping of STR alleles, therefore, was of high relevance during the last decades. Despite this, massively parallel sequencing (MPS) still lacks the analysis methods to fully utilize the information value of STRs in genome scale assays. Results: We propose an alignment-free algorithm, called Dante, for genotyping and characterization of STR alleles at user-specified known loci based on sequence reads originating from STR loci of interest. The method accounts for natural deviations from the expected sequence, such as variation in the repeat count, sequencing errors, ambiguous bases and complex loci containing several different motifs. In addition, we implemented a correction for copy number defects caused by the polymerase induced stutter effect as well as a prediction of STR expansions that, according to the conventional view, cannot be fully captured by inherently short MPS reads. We tested Dante on simulated datasets and on datasets obtained by targeted sequencing of protein coding parts of thousands of selected clinically relevant genes. In both these datasets, Dante outperformed HipSTR and GATK genotyping tools. Furthermore, Dante was able to predict allele expansions in all tested clinical cases. Availability and implementation: Dante is open source software, freely available for download at https://github.com/jbudis/dante. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.
4.
Nagyova, E; Radvanszky, J; Hyblova, M; Simovicova, V; Goncalvesova, E; Asselbergs, F W; Kadasi, L; Szemes, T; Minarik, G
Targeted next-generation sequencing in Slovak cardiomyopathy patients Journal Article
V: Bratislava Medical Journal, 120 (1), pp. 46-51, 2019, ISSN: 00069248.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Single nucleotide variants, Variant calling
@article{Nagyova201946,
title = {Targeted next-generation sequencing in Slovak cardiomyopathy patients},
author = {E Nagyova and J Radvanszky and M Hyblova and V Simovicova and E Goncalvesova and F W Asselbergs and L Kadasi and T Szemes and G Minarik},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060659545&doi=10.4149%2fBLL_2019_007&partnerID=40&md5=4242fb0c864e6c82fe2565c6cc094102},
doi = {10.4149/BLL_2019_007},
issn = {00069248},
year = {2019},
date = {2019-01-01},
journal = {Bratislava Medical Journal},
volume = {120},
number = {1},
pages = {46-51},
publisher = {Comenius University},
abstract = {OBJECTIVES: For the first time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identified candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C > T), ANKRD1 (c.683G > T), MYH7 (c.1025C > T), PKP2 (c.2003delA), TTN (c.51655C > T, c.84841G > T, c.101874_101881delAGAATTTG) have been detected for the first time and might represent Slovak- specific genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia. © AEPress s.r.o.},
keywords = {Genetic testing, Single nucleotide variants, Variant calling},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: For the first time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identified candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C > T), ANKRD1 (c.683G > T), MYH7 (c.1025C > T), PKP2 (c.2003delA), TTN (c.51655C > T, c.84841G > T, c.101874_101881delAGAATTTG) have been detected for the first time and might represent Slovak- specific genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia. © AEPress s.r.o.
2017
3.
Radvanszky, J; Hyblova, M; Durovcikova, D; Hikkelova, M; Fiedler, E; Kadasi, L; Turna, J; Minarik, G; Szemes, T
Complex phenotypes blur conventional borders between Say–Barber–Biesecker–Young–Simpson syndrome and genitopatellar syndrome Journal Article
V: Clinical Genetics, 91 (2), pp. 339-343, 2017, ISSN: 00099163.
Abstrakt | Linky | BibTeX | Značky: Case study, Genetic testing, Single nucleotide variants, Variant calling
@article{Radvanszky2017339,
title = {Complex phenotypes blur conventional borders between Say–Barber–Biesecker–Young–Simpson syndrome and genitopatellar syndrome},
author = {J Radvanszky and M Hyblova and D Durovcikova and M Hikkelova and E Fiedler and L Kadasi and J Turna and G Minarik and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84989325626&doi=10.1111%2fcge.12840&partnerID=40&md5=f3981a3dbb893dceec013f830ecf68f6},
doi = {10.1111/cge.12840},
issn = {00099163},
year = {2017},
date = {2017-01-01},
journal = {Clinical Genetics},
volume = {91},
number = {2},
pages = {339-343},
publisher = {Blackwell Publishing Ltd},
abstract = {Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd},
keywords = {Case study, Genetic testing, Single nucleotide variants, Variant calling},
pubstate = {published},
tppubtype = {article}
}
Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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.
Radvánszky, J; Minárik, G; Szemeš, T; Konečný, M; Kádaši, L
V: Lekarsky Obzor, 64 (11), pp. 418-427, 2015, ISSN: 04574214.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Review, Single nucleotide variants, Variant interpretation
@article{Radvánszky2015418,
title = {Interpretation of clinical significance of sequence variants in molecular genetics [Interpretácia klinického významu sekvenčných variantov v molekulovej genetike]},
author = {J Radvánszky and G Minárik and T Szemeš and M Konečný and L Kádaši},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020271195&partnerID=40&md5=bf647ff52f306470833ee835a42d012b},
issn = {04574214},
year = {2015},
date = {2015-01-01},
journal = {Lekarsky Obzor},
volume = {64},
number = {11},
pages = {418-427},
publisher = {Slovenska zdravotnicka univerzita},
abstract = {By applications of genomic analyses we are able to get an enormous number of different sequence variants in each analysed individual. From these only a small, although constantly growing, number of variants are already known and well characterised, while the majority of them are yet not characterised unknown variants. Their correct classification and interpretation are key factors for the understanding and usage of their informational value in clinical practice. Consistent education of professional staff able to handle, interpret and transfer the generated data to clinical workflow represents therefore a very important factor of professional practice. This article summarizes different recommendations for the evaluation and interpretation of sequence variants, from their correct nomenclature up to assigning them certain clinically relevant significance.},
keywords = {Genetic testing, Review, Single nucleotide variants, Variant interpretation},
pubstate = {published},
tppubtype = {article}
}
By applications of genomic analyses we are able to get an enormous number of different sequence variants in each analysed individual. From these only a small, although constantly growing, number of variants are already known and well characterised, while the majority of them are yet not characterised unknown variants. Their correct classification and interpretation are key factors for the understanding and usage of their informational value in clinical practice. Consistent education of professional staff able to handle, interpret and transfer the generated data to clinical workflow represents therefore a very important factor of professional practice. This article summarizes different recommendations for the evaluation and interpretation of sequence variants, from their correct nomenclature up to assigning them certain clinically relevant significance.