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  • Duplications of the critical Rubinstein–Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

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Original article
Duplications of the critical Rubinstein–Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome
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  1. Bernard Thienpont1,
  2. Frédérique Béna2,
  3. Jeroen Breckpot1,
  4. Nicole Philip3,
  5. Björn Menten4,
  6. Hilde Van Esch1,
  7. Emmanuel Scalais5,
  8. Jessica M Salamone6,
  9. Chin-To Fong6,
  10. Jennifer L Kussmann7,
  11. Dorothy K Grange8,
  12. Jerome L Gorski7,
  13. Farah Zahir9,
  14. Siu Li Yong10,
  15. Michael M Morris2,
  16. Stefania Gimelli2,
  17. Jean-Pierre Fryns1,
  18. Geert Mortier4,
  19. Jan M Friedman9,
  20. Laurent Villard11,
  21. Armand Bottani2,
  22. Joris R Vermeesch1,
  23. Sau Wai Cheung12,
  24. Koen Devriendt1
  1. 1Center for Human Genetics, K.U. Leuven, Leuven, Belgium
  2. 2Service of Genetic Medicine, Geneva University Hospitals, Geneva, Switzerland
  3. 3Centre de Référence Anomalies du Développement et Syndromes Malformatifs PACA, Département de génétique médicale, Hôpital d'Enfants de la Timone, Marseille, France
  4. 4Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
  5. 5Paediatric Neurology, Department of Paediatrics, Centre Hospitalier de Luxembourg, Luxembourg
  6. 6Departments of Pediatrics and of Medicine, University of Rochester, Rochester, New York, USA
  7. 7Department of Child Health, University of Missouri School of Medicine, Columbia, Missouri, USA
  8. 8Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital St. Louis, USA
  9. 9Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
  10. 10Medical Genetics Research Unit, Child and Family Research Institute, Children's and Women's Hospital, Vancouver, British Columbia, Canada
  11. 11Faculté de Médecine de La Timone, Université de la Méditerranée, Marseille, France
  12. 12Cytogenetic and Microarray Laboratories, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Professor Dr Koen Devriendt, Center for Human Genetics, K.U. Leuven, Herestraat 49 box 602, Leuven 3000, Belgium; koenraad.devriendt{at}uzleuven.be

Abstract

Background The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients.

Objectives To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis.

Results The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein–Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo.

Conclusions Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant.

  • Microduplication
  • CREBBP
  • Rubinstein–Taybi syndrome
  • genotype–phenotype correlation
  • arthrogryposis
  • genetics
  • cytogenetics

https://doi.org/10.1136/jmg.2009.070573

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    Footnotes

    • Funding Other funders: BT is supported by an IWT specialisatiebeurs; JB is an aspirant FWO; LV is supported by grants from Inserm and ANR Gis-Maladies Rares; NP is supported by PHRC 04-07; JMF's work was supported by a grant from Genome Canada. This work was made possible by grants from GOA/2006/12 and Center of Excellence SymBioSys (Research Council K.U.Leuven EF/05/007).

    • Competing interests None.

    • Ethics approval This study was conducted with the approval of the Etisch Commitee K.U.Leuven, Belgium.

    • Provenance and peer review Not commissioned; externally peer reviewed.