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Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects

Background: Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a chall...

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Autores principales: Bukowska-Olech, Ewelina, Sowińska-Seidler, Anna, Larysz, Dawid, Gawliński, Paweł, Koczyk, Grzegorz, Popiel, Delfina, Gurba-Bryśkiewicz, Lidia, Materna-Kiryluk, Anna, Adamek, Zuzanna, Szczepankiewicz, Aleksandra, Dominiak, Paweł, Glista, Filip, Matuszewska, Karolina, Jamsheer, Aleksander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112228/
https://www.ncbi.nlm.nih.gov/pubmed/35591945
http://dx.doi.org/10.3389/fmolb.2022.865494
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author Bukowska-Olech, Ewelina
Sowińska-Seidler, Anna
Larysz, Dawid
Gawliński, Paweł
Koczyk, Grzegorz
Popiel, Delfina
Gurba-Bryśkiewicz, Lidia
Materna-Kiryluk, Anna
Adamek, Zuzanna
Szczepankiewicz, Aleksandra
Dominiak, Paweł
Glista, Filip
Matuszewska, Karolina
Jamsheer, Aleksander
author_facet Bukowska-Olech, Ewelina
Sowińska-Seidler, Anna
Larysz, Dawid
Gawliński, Paweł
Koczyk, Grzegorz
Popiel, Delfina
Gurba-Bryśkiewicz, Lidia
Materna-Kiryluk, Anna
Adamek, Zuzanna
Szczepankiewicz, Aleksandra
Dominiak, Paweł
Glista, Filip
Matuszewska, Karolina
Jamsheer, Aleksander
author_sort Bukowska-Olech, Ewelina
collection PubMed
description Background: Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a challenging diagnostic issue. Methods: We investigated a three-tiered approach (karyotyping, Sanger sequencing, followed by custom gene panel/chromosomal microarray analysis, and exome sequencing), coupled with prioritization of variants based on dysmorphological assessment and description in terms of human phenotype ontology. In addition, we have also performed a statistical analysis of the obtained clinical data using the nonparametric test χ(2). Results: We achieved a 43% diagnostic success rate and have demonstrated the complexity of mutations’ type harbored by the patients, which were either chromosomal aberrations, copy number variations, or point mutations. The majority of pathogenic variants were found in the well-known CS genes, however, variants found in genes associated with chromatinopathies or RASopathies are of particular interest. Conclusion: We have critically summarized and then optimised a cost-effective diagnostic algorithm, which may be helpful in a daily diagnostic routine and future clinical research of various CS types. Moreover, we have pinpointed the possible underestimated co-occurrence of CS and intellectual disability, suggesting it may be overlooked when intellectual disability constitutes a primary clinical complaint. On the other hand, in any case of already detected syndromic CS and intellectual disability, the possible occurrence of clinical features suggestive for chromatinopathies or RASopathies should also be considered.
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spelling pubmed-91122282022-05-18 Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects Bukowska-Olech, Ewelina Sowińska-Seidler, Anna Larysz, Dawid Gawliński, Paweł Koczyk, Grzegorz Popiel, Delfina Gurba-Bryśkiewicz, Lidia Materna-Kiryluk, Anna Adamek, Zuzanna Szczepankiewicz, Aleksandra Dominiak, Paweł Glista, Filip Matuszewska, Karolina Jamsheer, Aleksander Front Mol Biosci Molecular Biosciences Background: Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a challenging diagnostic issue. Methods: We investigated a three-tiered approach (karyotyping, Sanger sequencing, followed by custom gene panel/chromosomal microarray analysis, and exome sequencing), coupled with prioritization of variants based on dysmorphological assessment and description in terms of human phenotype ontology. In addition, we have also performed a statistical analysis of the obtained clinical data using the nonparametric test χ(2). Results: We achieved a 43% diagnostic success rate and have demonstrated the complexity of mutations’ type harbored by the patients, which were either chromosomal aberrations, copy number variations, or point mutations. The majority of pathogenic variants were found in the well-known CS genes, however, variants found in genes associated with chromatinopathies or RASopathies are of particular interest. Conclusion: We have critically summarized and then optimised a cost-effective diagnostic algorithm, which may be helpful in a daily diagnostic routine and future clinical research of various CS types. Moreover, we have pinpointed the possible underestimated co-occurrence of CS and intellectual disability, suggesting it may be overlooked when intellectual disability constitutes a primary clinical complaint. On the other hand, in any case of already detected syndromic CS and intellectual disability, the possible occurrence of clinical features suggestive for chromatinopathies or RASopathies should also be considered. Frontiers Media S.A. 2022-04-28 /pmc/articles/PMC9112228/ /pubmed/35591945 http://dx.doi.org/10.3389/fmolb.2022.865494 Text en Copyright © 2022 Bukowska-Olech, Sowińska-Seidler, Larysz, Gawliński, Koczyk, Popiel, Gurba-Bryśkiewicz, Materna-Kiryluk, Adamek, Szczepankiewicz, Dominiak, Glista, Matuszewska and Jamsheer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Bukowska-Olech, Ewelina
Sowińska-Seidler, Anna
Larysz, Dawid
Gawliński, Paweł
Koczyk, Grzegorz
Popiel, Delfina
Gurba-Bryśkiewicz, Lidia
Materna-Kiryluk, Anna
Adamek, Zuzanna
Szczepankiewicz, Aleksandra
Dominiak, Paweł
Glista, Filip
Matuszewska, Karolina
Jamsheer, Aleksander
Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title_full Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title_fullStr Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title_full_unstemmed Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title_short Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
title_sort results from genetic studies in patients affected with craniosynostosis: clinical and molecular aspects
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112228/
https://www.ncbi.nlm.nih.gov/pubmed/35591945
http://dx.doi.org/10.3389/fmolb.2022.865494
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