RT Journal Article
SR Electronic
T1 Duplications of the critical Rubinstein–Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 155
OP 161
DO 10.1136/jmg.2009.070573
VO 47
IS 3
A1 Thienpont, Bernard
A1 Béna, Frédérique
A1 Breckpot, Jeroen
A1 Philip, Nicole
A1 Menten, Björn
A1 Van Esch, Hilde
A1 Scalais, Emmanuel
A1 Salamone, Jessica M
A1 Fong, Chin-To
A1 Kussmann, Jennifer L
A1 Grange, Dorothy K
A1 Gorski, Jerome L
A1 Zahir, Farah
A1 Yong, Siu Li
A1 Morris, Michael M
A1 Gimelli, Stefania
A1 Fryns, Jean-Pierre
A1 Mortier, Geert
A1 Friedman, Jan M
A1 Villard, Laurent
A1 Bottani, Armand
A1 Vermeesch, Joris R
A1 Cheung, Sau Wai
A1 Devriendt, Koen
YR 2010
UL http://jmg.bmj.com/content/47/3/155.abstract
AB 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.