Spolupracovali sme na publikáciach
2021
3.
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.
2017
2.
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
1.
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.