Nonsyndromic craniosynostosis: novel coding variants - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Pediatric Research Année : 2019

Nonsyndromic craniosynostosis: novel coding variants

Résumé

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). 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.
Fichier principal
Vignette du fichier
2019_Sewda_hal.pdf (640.9 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02322180 , version 1 (11-01-2021)

Identifiants

Citer

Anshuman Sewda, Sierra White, Monica Erazo, Ke Hao, Gemma García-Fructuoso, et al.. Nonsyndromic craniosynostosis: novel coding variants. Pediatric Research, 2019, 85 (4), pp.463-468. ⟨10.1038/s41390-019-0274-2⟩. ⟨hal-02322180⟩
78 Consultations
69 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More