Nonsyndromic craniosynostosis: novel coding variants.
Por:
Sewda A, White SR, Erazo M, Hao K, García-Fructuoso G, Fernández-Rodriguez I, Heuzé Y, Richtsmeier JT, Romitti PA, Reva B, Jabs EW and Peter I
Publicada:
1 mar 2019
Ahead of Print:
14 ene 2019
Categoría:
Pediatrics, perinatology and child health
Resumen:
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.
Filiaciones:
Sewda A:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
White SR:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Erazo M:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Hao K:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
García-Fructuoso G:
Department of Pediatric Neurosurgery, Hospital Sant Joan de Déu, Barcelona, Spain
Fernández-Rodriguez I:
Department of Pediatric Neurosurgery, Hospital Sant Joan de Déu, Barcelona, Spain
Heuzé Y:
University Bordeaux, CNRS, MCC, PACEA, UMR5199, Bordeaux Archaeological Sciences Cluster of Excellence, Pessac, France
Richtsmeier JT:
Department of Anthropology, Pennsylvania State University, University Park, PA, USA
Romitti PA:
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA
Reva B:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Jabs EW:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Peter I:
Department of Genetics Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Open Access
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