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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
MDPI
2023
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| _version_ | 1797109867865964544 |
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| author | Tooze, RS Calpena, E Weber, A Wilson, LC Twigg, SRF Wilkie, AOM |
| author_facet | Tooze, RS Calpena, E Weber, A Wilson, LC Twigg, SRF Wilkie, AOM |
| author_sort | Tooze, RS |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T07:47:20Z |
| format | Journal article |
| id | oxford-uuid:abd10577-0f0d-47cb-81cd-f5b15cd08a42 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:47:20Z |
| publishDate | 2023 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:abd10577-0f0d-47cb-81cd-f5b15cd08a422023-06-16T13:28:03ZReview of recurrently mutated genes in craniosynostosis supports expansion of diagnostic gene panelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:abd10577-0f0d-47cb-81cd-f5b15cd08a42EnglishSymplectic ElementsMDPI2023Tooze, RSCalpena, EWeber, AWilson, LCTwigg, SRFWilkie, AOMCraniosynostosis, 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. |
| spellingShingle | Tooze, RS Calpena, E Weber, A Wilson, LC Twigg, SRF Wilkie, AOM 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 |
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