Somatic FGFR and TWIST Mutations are not a Common Cause of Isolated Nonsyndromic Single Suture Craniosynostosis
Abstract
Pathogenic mutations in FGFR2 and TWIST genes are detected in the majority of individuals with Crouzon, Pfeiffer, Apert, and Saethre-Chotzen syndromes. In contrast, mutations have been identified rarely in cases of nonsyndromic, single suture craniosynostosis. Recently, two studies confirming somatic mosaicism with local expression of an FGFR mutation have been reported. This study investigates whether somatic mosaicism could account for nonsyndromic, single suture craniosynostosis. Eight individuals with single suture craniosynostosis who were negative for known mutations in FGFR1-3 and TWIST after screening in their leucocyte DNA were tested for the presence of pathogenic mutations in suture cell-derived DNA. Five had sagittal synostosis, two had metopic synostosis, and the other unicoronal synostosis. Osteoprogenitor cells from surgically excised fusing sutures and an adjacent open suture were cultured. DNA from the cultured cells grown to passage 3 was then examined for underlying FGFR and TWIST mutations. No mutations within the exons of the FGFR or TWIST genes studied were identified in any suture cells. This study found no evidence to support the notion that mosaicism for FGFR or TWIST mutations, normally associated with syndromal forms of craniosynostosis, occur in single suture craniosynostosis. Thus, any underlying genetic defects must occur in regions outside those normally implicated in syndromal craniosynostosis, or this disorder could arise as a consequence of some other epigenetic modification.
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Synonymous or common variants of FGFR3 have not shown clear pathogenic relevance in sCS.
“In contrast, synonymous or common variants of FGFR3 have not shown clear pathogenic relevance, emphasizing the need to distinguish true disease-associated findings from background polymorphisms [23, 42].”
From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [42]
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- Authors
- Anderson, P. J., Cox, T. C., Roscioli, T., Elakis, G., Smithers, L., David, D. J., & Powell, B.
- Affiliations
- University of South Australia (AU)
- Monash University (AU)
- Prince of Wales Hospital (AU)
- Women's and Children's Hospital (AU)
- Corresponding author
- Anderson, Peter J.
- David, David J.
- Powell, Barry
- Venue
- Journal of Craniofacial Surgery
- Published
- 2007-03
- Volume
- 18
- Issue
- 2
- Pages
- 312-314
- ISSN
- 1049-2275 (ISSN-L)
- OpenAlex
- W2004893262
- Cited by
- 23
- References
- 11
- Citations by year
- 2026: 4 · 2024: 2 · 2023: 1 · 2021: 2 · 2019: 1 · 2017: 2 · 2016: 2 · 2012: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Craniofacial Surgery (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- nonsyndromic craniosynostosis, single-suture craniosynostosis, FGFR mutations, somatic mosaicism, FGFR2, FGFR1, FGFR3, sagittal synostosis, metopic synostosis, unicoronal synostosis, osteoprogenitor cells, epigenetic modifications
- MeSH terms
- Cells, Cultured, Craniosynostoses, DNA Mutational Analysis, Female, Humans, Male, Mosaicism, Mutation, Receptors, Fibroblast Growth Factor, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 2, Receptor, Fibroblast Growth Factor, Type 3, Twist-Related Protein 1
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