Characterization of 14 novel deletions underlying Rubinstein–Taybi syndrome: an update of the CREBBP deletion repertoire
Rubinstein–Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55 % of cases) and EP300 (~8 %) genes. The CREBBP mutational spectru...
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Published in | Human genetics Vol. 134; no. 6; pp. 613 - 626 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.06.2015
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Rubinstein–Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the
CREBBP
(~55 % of cases) and
EP300
(~8 %) genes. The
CREBBP
mutational spectrum is variegated and characterized by point mutations (30–50 %) and deletions (~10 %). The latter are diverse in size and genomic position and remove either the whole
CREBBP
gene and its flanking regions or only an intragenic portion. Here, we report 14 novel
CREBBP
deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecular techniques: fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and array comparative genome hybridization, to a large cohort of RSTS patients. Deletions involving
CREBBP
account for 23 % of our detected
CREBBP
mutations, making an important contribution to the mutational spectrum. Genotype–phenotype correlations revealed that patients with
CREBBP
deletions extending beyond this gene did not always have a more severe phenotype than patients harboring
CREBBP
point mutations, suggesting that neighboring genes play only a limited role in the etiopathogenesis of
CREBBP
-centerd contiguous gene syndrome. Accordingly, the extent of the deletion is not predictive of the severity of the clinical phenotype. |
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ISSN: | 0340-6717 1432-1203 |
DOI: | 10.1007/s00439-015-1542-9 |