TY - JOUR
T1 - Duplications of the critical Rubinstein - Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome
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
PY - 2010/3
Y1 - 2010/3
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=77949712474&partnerID=8YFLogxK
U2 - 10.1136/jmg.2009.070573
DO - 10.1136/jmg.2009.070573
M3 - Article
C2 - 19833603
AN - SCOPUS:77949712474
SN - 0022-2593
VL - 47
SP - 155
EP - 161
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 3
ER -