Nonsyndromic craniosynostosis: novel coding variants.
Pediatr Res
; 85(4): 463-468, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30651579
ABSTRACT
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>Gp.(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>Tp.(Glu105*) variant in EFNB1 and c.435G>Cp.(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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Craniossinostoses
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos