Journal article
Nonsyndromic craniosynostosis: novel coding variants
Pediatric research, Vol.85(4), pp.463-468
03/2019
DOI: 10.1038/s41390-019-0274-2
PMCID: PMC6398438
PMID: 30651579
Abstract
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.
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).
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.
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.
Details
- Title: Subtitle
- Nonsyndromic craniosynostosis: novel coding variants
- Creators
- Anshuman Sewda - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. anshuman.sewda@mssm.eduSierra R White - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAMonica Erazo - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAKe Hao - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAGemma García-Fructuoso - Department of Pediatric Neurosurgery, Hospital Sant Joan de Déu, Barcelona, SpainIvette Fernández-Rodriguez - Department of Pediatric Neurosurgery, Hospital Sant Joan de Déu, Barcelona, SpainYann Heuzé - University Bordeaux, CNRS, MCC, PACEA, UMR5199, Bordeaux Archaeological Sciences Cluster of Excellence, Pessac, FranceJoan T Richtsmeier - Department of Anthropology, Pennsylvania State University, University Park, PA, USAPaul A Romitti - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USABoris Reva - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAEthylin Wang Jabs - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInga Peter - Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.85(4), pp.463-468
- Publisher
- United States
- DOI
- 10.1038/s41390-019-0274-2
- PMID
- 30651579
- PMCID
- PMC6398438
- ISSN
- 1530-0447
- eISSN
- 1530-0447
- Grant note
- R01 DD000350 / NCBDD CDC HHS P01 HD078233 / NICHD NIH HHS U01DD001035 / ACL HHS S10 OD018522 / NIH HHS U01 DD001035 / NCBDD CDC HHS U01 DD001223 / NCBDD CDC HHS
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983995049402771
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