Large genomic rearrangements in NIPBL are infrequent in Cornelia de Lange syndrome

Eur J Hum Genet. 2007 Apr;15(4):505-8. doi: 10.1038/sj.ejhg.5201776. Epub 2007 Jan 31.


Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, malformations of the upper limbs, and delay in growth and development. Mutations in NIPBL are associated with CdLS in 27-56% of cases and have been reported as point mutations, small insertions and deletions in coding regions, regulatory regions and at splice junctions. All previous studies used PCR-based exon-scanning methodologies that do not allow detection of large genomic rearrangements. We studied the relative copy number of NIPBL exons in a series of 50 CdLS probands, negative for NIPBL mutations, by multiplex ligation-dependent probe amplification (MLPA). In a single patient, we found a 5.2 kb deletion encompassing exons 41-42 of NIPBL. Our studies indicate that large NIPBL rearrangements do occur in CdLS but are likely to be infrequent events.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 9 / genetics
  • Cohort Studies
  • DNA Mutational Analysis / methods
  • De Lange Syndrome / genetics*
  • Exons / genetics*
  • Female
  • Gene Deletion*
  • Gene Rearrangement*
  • Genome, Human
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Nucleic Acid Amplification Techniques / methods
  • Pedigree
  • Phenotype
  • Proteins / genetics*


  • Cell Cycle Proteins
  • NIPBL protein, human
  • Proteins