Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome.
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.
Thienpont
Bernard
B
Center for Human Genetics, K.U. Leuven, Herestraat 49 box 602, Leuven 3000, Belgium.
Béna
Frédérique
F
Breckpot
Jeroen
J
Philip
Nicole
N
Menten
Björn
B
Van Esch
Hilde
H
Scalais
Emmanuel
E
Salamone
Jessica M
JM
Fong
Chin-To
CT
Kussmann
Jennifer L
JL
Grange
Dorothy K
DK
Gorski
Jerome L
JL
Zahir
Farah
F
Yong
Siu Li
SL
Morris
Michael M
MM
Gimelli
Stefania
S
Fryns
Jean-Pierre
JP
Mortier
Geert
G
Friedman
Jan M
JM
Villard
Laurent
L
Bottani
Armand
A
Vermeesch
Joris R
JR
Cheung
Sau Wai
SW
Devriendt
Koen
K
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
D050882:CREB-Binding Protein; C494363:CREBBP protein, human