Nonsyndromic craniosynostosis: novel coding variants

Anshuman Sewda, Sierra R. White, Monica Erazo, Ke Hao, Gemma García-Fructuoso, Ivette Fernández-Rodriguez, Yann Heuzé, Joan T. Richtsmeier, Paul A. Romitti, Boris Reva, Ethylin Wang Jabs, Inga Peter

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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 5 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.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalPediatric Research
Issue number4
StatePublished - Mar 1 2019

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health


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