Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR

Hum Mutat. 2004 Mar;23(3):278-84. doi: 10.1002/humu.20001.


Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome characterized by facial abnormalities, broad thumbs, broad big toes, and growth and mental retardation as the main clinical features. RTS was shown to be associated with disruption of the CREB-binding protein gene CBP (CREBBP), either by gross chromosomal rearrangements or by point mutations. Translocations and inversions involving chromosome band 16p13.3 form the minority of CBP mutations, whereas microdeletions occur more frequently (about 10%). Most deletion studies in RTS are performed by FISH analysis, and five cosmids must be used to cover the whole of the CBP gene, which spreads over 150 kb. Here we report the design of gene dosage assays by real-time quantitative PCR that are targeted on three exons located respectively at the 5' end (exon 2), in the middle (exon 12), and at the 3' end (exon 30) of the CBP gene. This technique proved to be efficient and powerful in finding deletions and complementary to the other available techniques, since it allowed us to identify deletions at the 3' end of the gene that had been missed by FISH analysis, and to refine some deletion breakpoints. Our results therefore suggest that real-time quantitative PCR is a useful technique to be included in the deletion search in RTS patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • CREB-Binding Protein
  • Computer Systems*
  • Exons / genetics
  • Female
  • Gene Deletion*
  • Gene Dosage
  • Genetic Markers / genetics
  • Heterozygote
  • Humans
  • Male
  • Microsatellite Repeats / genetics
  • Nuclear Proteins / genetics*
  • Phenotype
  • Polymerase Chain Reaction / methods*
  • Rubinstein-Taybi Syndrome / genetics*
  • Trans-Activators / genetics*


  • Genetic Markers
  • Nuclear Proteins
  • Trans-Activators
  • CREB-Binding Protein
  • CREBBP protein, human