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Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels
Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant in one of just seven genes or have a chromosomal abnormality, over 60 genes are known to be recurrently mutated, thus comprising a l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048212/ https://www.ncbi.nlm.nih.gov/pubmed/36980886 http://dx.doi.org/10.3390/genes14030615 |
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author | Tooze, Rebecca S. Calpena, Eduardo Weber, Astrid Wilson, Louise C. Twigg, Stephen R. F. Wilkie, Andrew O. M. |
author_facet | Tooze, Rebecca S. Calpena, Eduardo Weber, Astrid Wilson, Louise C. Twigg, Stephen R. F. Wilkie, Andrew O. M. |
author_sort | Tooze, Rebecca S. |
collection | PubMed |
description | Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant in one of just seven genes or have a chromosomal abnormality, over 60 genes are known to be recurrently mutated, thus comprising a long tail of rarer diagnoses. Genome sequencing for the diagnosis of rare diseases is increasingly used in clinical settings, but analysis of the data is labor intensive and involves a trade-off between achieving high sensitivity or high precision. PanelApp, a crowd-sourced disease-focused set of gene panels, was designed to enable prioritization of variants in known disease genes for a given pathology, allowing enhanced identification of true-positives. For heterogeneous disorders like craniosynostosis, these panels must be regularly updated to ensure that diagnoses are not being missed. We provide a systematic review of genetic literature on craniosynostosis over the last 5 years, including additional results from resequencing a 42-gene panel in 617 affected individuals. We identify 16 genes (representing a 25% uplift) that should be added to the list of bona fide craniosynostosis disease genes and discuss the insights that these new genes provide into pathophysiological mechanisms of craniosynostosis. |
format | Online Article Text |
id | pubmed-10048212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100482122023-03-29 Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels Tooze, Rebecca S. Calpena, Eduardo Weber, Astrid Wilson, Louise C. Twigg, Stephen R. F. Wilkie, Andrew O. M. Genes (Basel) Article Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant in one of just seven genes or have a chromosomal abnormality, over 60 genes are known to be recurrently mutated, thus comprising a long tail of rarer diagnoses. Genome sequencing for the diagnosis of rare diseases is increasingly used in clinical settings, but analysis of the data is labor intensive and involves a trade-off between achieving high sensitivity or high precision. PanelApp, a crowd-sourced disease-focused set of gene panels, was designed to enable prioritization of variants in known disease genes for a given pathology, allowing enhanced identification of true-positives. For heterogeneous disorders like craniosynostosis, these panels must be regularly updated to ensure that diagnoses are not being missed. We provide a systematic review of genetic literature on craniosynostosis over the last 5 years, including additional results from resequencing a 42-gene panel in 617 affected individuals. We identify 16 genes (representing a 25% uplift) that should be added to the list of bona fide craniosynostosis disease genes and discuss the insights that these new genes provide into pathophysiological mechanisms of craniosynostosis. MDPI 2023-02-28 /pmc/articles/PMC10048212/ /pubmed/36980886 http://dx.doi.org/10.3390/genes14030615 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tooze, Rebecca S. Calpena, Eduardo Weber, Astrid Wilson, Louise C. Twigg, Stephen R. F. Wilkie, Andrew O. M. Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title | Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title_full | Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title_fullStr | Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title_full_unstemmed | Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title_short | Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels |
title_sort | review of recurrently mutated genes in craniosynostosis supports expansion of diagnostic gene panels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048212/ https://www.ncbi.nlm.nih.gov/pubmed/36980886 http://dx.doi.org/10.3390/genes14030615 |
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