Objective: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS).
Methods: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing.
Results: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected.
Conclusion: The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.