Human Genetics

, Volume 120, Issue 2, pp 179–186

Evidence for a new contiguous gene syndrome, the chromosome 16p13.3 deletion syndrome alias severe Rubinstein–Taybi syndrome

  • Oliver Bartsch
  • Sasan Rasi
  • Alicia Delicado
  • Sarah Dyack
  • Luitgard M. Neumann
  • Eva Seemanová
  • Marianne Volleth
  • Thomas Haaf
  • Vera M. Kalscheuer
Original Investigation

DOI: 10.1007/s00439-006-0215-0

Cite this article as:
Bartsch, O., Rasi, S., Delicado, A. et al. Hum Genet (2006) 120: 179. doi:10.1007/s00439-006-0215-0

Abstract

Rubinstein–Taybi syndrome (RSTS) is a well-known autosomal dominant mental retardation syndrome with typical facial and skeletal abnormalities. Previously, we have reported two patients presenting with RSTS and additional clinical features including failure to thrive, seizures, and intractable infections (Bartsch et al. in Eur J Hum Genet 7:748–756, 1999). Recently we identified a third patient with this condition, termed here severe RSTS, or chromosome 16p13.3 deletion syndrome. The three patients died in infancy, and all displayed a specific mutation, a chromosomal microdeletion including the 3′-end of the CREBBP gene. Using fluorescence in situ hybridization and closely spaced DNA probes, we characterized the deletion intervals in these patients and in three individuals with a deletion of CREBBP and typical RSTS. The deleted DNA segments were found to greatly vary in size, spanning from ∼40 kb to >3 Mb. Four individuals, including the patients with severe RSTS, exhibited deletions containing gene/s in addition to CREBBP. The patients with severe RSTS all had deletions comprising telomeric neighbor genes of CREBBP, including DNASE1, a dominant gene encoding a nuclease that has been associated with systemic lupus erythematodes. Our findings suggest that severe RSTS is distinct from RSTS and represents a novel true contiguous gene syndrome (chromosome 16p13.3 deletion syndrome). Because of the risk of critical infections and high mortality rate, we recommend that the size of the deletion interval should be determined in CREBBP deletion-positive patients with RSTS, especially in young children. Further studies are needed to delineate the clinical spectrum of the new disorder and to clarify the role of DNASE1.

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Oliver Bartsch
    • 1
  • Sasan Rasi
    • 1
  • Alicia Delicado
    • 2
  • Sarah Dyack
    • 3
  • Luitgard M. Neumann
    • 4
  • Eva Seemanová
    • 5
  • Marianne Volleth
    • 6
  • Thomas Haaf
    • 1
  • Vera M. Kalscheuer
    • 7
  1. 1.Institute for Human GeneticsMainz University School of MedicineMainzGermany
  2. 2.Genética Médica Hospital Universitario “La Paz”MadridSpain
  3. 3.IWK Health CentreDalhousie UniversityHalifaxCanada
  4. 4.Institute of Human GeneticsCharité Campus Virchow-KlinikumBerlinGermany
  5. 5.Institute of Medical Biology and Genetics, 2nd Medical SchoolCharles UniversityPrague 5Czech Republic
  6. 6.Institute for Human GeneticsOtto von Guericke UniversityMagdeburgGermany
  7. 7.Max-Planck Institute for Molecular GeneticsBerlinGermany