title: Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Center for Human Genetics, K.U. Leuven, Herestraat 49 box 602, Leuven 3000, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thienpont
authors.forename: Frédérique
authors.initials: F
authors.lastname: Béna
authors.forename: Jeroen
authors.initials: J
authors.lastname: Breckpot
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scalais
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Salamone
authors.forename: Chin-To
authors.initials: CT
authors.lastname: Fong
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kussmann
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Gorski
authors.forename: Farah
authors.initials: F
authors.lastname: Zahir
authors.forename: Siu Li
authors.initials: SL
authors.lastname: Yong
authors.forename: Michael M
authors.initials: MM
authors.lastname: Morris
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Jan M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
authors.forename: Armand
authors.initials: A
authors.lastname: Bottani
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D050882:CREB-Binding Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics*; D013577:Syndrome
chemical_list: D050882:CREB-Binding Protein; C494363:CREBBP protein, human