Identification and functional validation of pathogenic small nucleotide variants in patients with craniosynostosis

ABSTRACT

Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2,000 live births. It is a heterogenous disorder with documented monogenic, polygenic, chromosomal, and environmental causes. Although many patients with a genetically determined cause harbour a variant in one of just seven genes, or have a chromosomal abnormality, there is a long tail of rarer genetic diagnoses with over 60 genes known to be recurrently mutated. Despite the recent uplift in knowledge of the genetic