[Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome]

Area of Science:

• Genetics and Genomics
• Developmental Biology
• Clinical Medicine

Context:

• Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by distinctive facial features, growth delays, and intellectual disability.
• Accurate genetic diagnosis is crucial for understanding CdLS pathogenesis and providing appropriate patient care.
• Previous studies have identified several genes associated with CdLS, but the genetic landscape remains incompletely understood.

Purpose:

• To investigate the clinical phenotypes of three children with suspected Cornelia de Lange syndrome (CdLS).
• To perform genetic testing using next-generation sequencing to identify causative variants.
• To expand the spectrum of known pathogenic variants associated with CdLS.

Summary:

• Three children presenting with typical CdLS features underwent whole exome sequencing.
• Genetic analysis revealed de novo pathogenic variants in NIPBL (child 1), SMC1A (child 2), and HDAC8 (child 3).
• The NIPBL and HDAC8 variants identified are novel, contributing new information to the genetic basis of CdLS.

Impact:

• This study expands the mutational spectrum of Cornelia de Lange syndrome, particularly highlighting novel variants in NIPBL and HDAC8.
• The findings contribute to a more comprehensive understanding of the genetic underpinnings of CdLS.
• Enriching the spectrum of pathogenic variants aids in improving diagnostic accuracy and genetic counseling for families affected by CdLS.