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

Bernard Thienpont, Frédérique Béna, Jeroen Breckpot, Nicole Philip, Björn Menten, Hilde Van Esch, Emmanuel Scalais, Jessica M. Salamone, Chin To Fong, Jennifer L. Kussmann, Dorothy K. Grange, Jerome L. Gorski, Farah Zahir, Siu Li Yong, Michael M. Morris, Stefania Gimelli, Jean Pierre Fryns, Geert Mortier, Jan M. Friedman, Laurent VillardArmand Bottani, Joris R. Vermeesch, Sau Wai Cheung, Koen Devriendt

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalJournal of Medical Genetics
Volume47
Issue number3
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

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Chromosomes
Phenotype
Rubinstein-Taybi Syndrome
Genotype
Genetic Fitness
Arthrogryposis
Karyotyping
Inborn Genetic Diseases
Genitalia
Palate
Thumb
Growth and Development
Technology
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Duplications of the critical Rubinstein - Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome. / Thienpont, Bernard; Béna, Frédérique; Breckpot, Jeroen; Philip, Nicole; Menten, Björn; Van Esch, Hilde; Scalais, Emmanuel; Salamone, Jessica M.; Fong, Chin To; Kussmann, Jennifer L.; Grange, Dorothy K.; Gorski, Jerome L.; Zahir, Farah; Yong, Siu Li; Morris, Michael M.; Gimelli, Stefania; Fryns, Jean Pierre; Mortier, Geert; Friedman, Jan M.; Villard, Laurent; Bottani, Armand; Vermeesch, Joris R.; Cheung, Sau Wai; Devriendt, Koen.

In: Journal of Medical Genetics, Vol. 47, No. 3, 03.2010, p. 155-161.

Research output: Contribution to journalArticle

Thienpont, B, Béna, F, Breckpot, J, Philip, N, Menten, B, Van Esch, H, Scalais, E, Salamone, JM, Fong, CT, Kussmann, JL, Grange, DK, Gorski, JL, Zahir, F, Yong, SL, Morris, MM, Gimelli, S, Fryns, JP, Mortier, G, Friedman, JM, Villard, L, Bottani, A, Vermeesch, JR, Cheung, SW & Devriendt, K 2010, 'Duplications of the critical Rubinstein - Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome', Journal of Medical Genetics, vol. 47, no. 3, pp. 155-161. https://doi.org/10.1136/jmg.2009.070573
Thienpont, Bernard ; Béna, Frédérique ; Breckpot, Jeroen ; Philip, Nicole ; Menten, Björn ; Van Esch, Hilde ; Scalais, Emmanuel ; Salamone, Jessica M. ; Fong, Chin To ; Kussmann, Jennifer L. ; Grange, Dorothy K. ; Gorski, Jerome L. ; Zahir, Farah ; Yong, Siu Li ; Morris, Michael M. ; Gimelli, Stefania ; Fryns, Jean Pierre ; Mortier, Geert ; Friedman, Jan M. ; Villard, Laurent ; Bottani, Armand ; Vermeesch, Joris R. ; Cheung, Sau Wai ; Devriendt, Koen. / Duplications of the critical Rubinstein - Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome. In: Journal of Medical Genetics. 2010 ; Vol. 47, No. 3. pp. 155-161.
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AU - Thienpont, Bernard

AU - Béna, Frédérique

AU - Breckpot, Jeroen

AU - Philip, Nicole

AU - Menten, Björn

AU - Van Esch, Hilde

AU - Scalais, Emmanuel

AU - Salamone, Jessica M.

AU - Fong, Chin To

AU - Kussmann, Jennifer L.

AU - Grange, Dorothy K.

AU - Gorski, Jerome L.

AU - Zahir, Farah

AU - Yong, Siu Li

AU - Morris, Michael M.

AU - Gimelli, Stefania

AU - Fryns, Jean Pierre

AU - Mortier, Geert

AU - Friedman, Jan M.

AU - Villard, Laurent

AU - Bottani, Armand

AU - Vermeesch, Joris R.

AU - Cheung, Sau Wai

AU - Devriendt, Koen

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N2 - 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.

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