Clinical and genetic features of syndromic craniosynostosis in 18 Chinese probands: novel candidate genes and phenotypes of known pathogenic genes
Introduction Craniosynostosis is a common congenital disorder characterized by premature fusion of one or more cranial sutures, categorized into non-syndromic (NSCS) and syndromic craniosynostosis (SCS). SCS accounts for ∼30% of cases, often accompanied by severe clinical complications, with 20%–25% of patients lacking a clear molecular etiology. Methods We enrolled 18 Chinese SCS patients and analyzed their clinical and genetic data via whole-exome sequencing (WES), copy number variation (CNV) analysis, and Sanger sequencing validation. Results We identified 15 single nucleotide variants, 2 insertions/deletions, and one microdeletion at 11q23.3q25. Thirteen probands harbored pathogenic/likely pathogenic variants in known craniosynostosis-related genes: FGFR2 (n = 4), FGFR3 (n = 2), TWIST1 (n = 2), and one each in ERF, EFNB1, SON, HUWE1, and KRAS. Three probands carried variants in PTEN, SRCAP, PQBP1, none of which have previously been associated with craniosynostosis. Notably, a de novo nonsense variant (c.562G>T, p. Glu188Ter) was identified in NOG, a promising candidate gene for craniosynostosis. Discussion Our findings broaden the genotypic spectrum of craniosynostosis and further highlight the genetic heterogeneity underlying this disorder. The discovery of variants in PTEN, SRCAP, PQBP1, and NOG identifies novel candidate genes and uncovers potential disease mechanisms.