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Nonsyndromic Craniosynostosis: Novel Coding Variants
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January 14 2019
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Source: Pediatr Res. 85(4):463-468
[PDF-640.90 KB]
Details:
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Alternative Title:Pediatr Res
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Personal Author:
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Description:Background
Craniosynostosis (CS), the premature fusion of one or more neurocranial sutures, is associated with approximately 200 syndromes; however, about 65%−85% of patients present with no additional major birth defects.
Methods
We conducted targeted next-generation sequencing of 60 known syndromic and other candidate genes in patients with sagittal nonsyndromic CS (sNCS, n=40) and coronal nonsyndromic CS (cNCS, n=19).
Results
We identified 18 previously published and five novel pathogenic variants, including three de novo variants. Novel variants included a paternally-inherited c.2209C>G:p.(Leu737Val) variant in BBS9 of a patient with cNCS. Common variants in BBS9, a gene required for ciliogenesis during cranial suture development, have been associated with sNCS risk in a previous genome-wide association study. We also identified c.313G>T:p.(Glu105*) variant in EFNB1 and c.435G>C:p.(Lys145Asn) variant in TWIST1, both in patients with cNCS. Mutations in EFNB1 and TWIST1 have been linked to craniofrontonasal and Saethre-Chotzen syndrome, respectively; both present with coronal CS.
Conclusions
We provide additional evidence that variants in genes implicated in syndromic CS play a role in isolated CS, supporting their inclusion in genetic panels for screening patients with NCS. We also identified a novel BBS9 variant that further shows the potential involvement of BBS9 in the pathogenesis of CS.
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Pubmed ID:30651579
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Pubmed Central ID:PMC6398438
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Funding:
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Volume:85
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Issue:4
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