Submicroscopic deletion of chromosome 16p13.3 in patients with Rubinstein-Taybi syndrome

Abstract

The Rubinstein-Taybi syndrome (RTS) is a well-defined entity characterized by growth and mental retardation, broad thumbs and halluces, and typical face. The RTS locus was assigned to 16p13.3, and interstitial submicroscopic deletions of this region (RT1 cosmid, D16S237) were initially identified in 25% of RTS patients. The gene for the human CREB binding protein, the transcriptional coactivator CBP, is included in the RT1 cosmid, and mutations in CBP have recently been identified in nondeleted RTS patients. We investigated 30 French patients with RTS. Among these patients, 3 had the RT1 microdeletion (frequency 10%). There is no obvious phenotypic difference between the patients with and without the RT1 deletion. The RT1 probe appears useful for confirmation of the diagnosis but is of little interest as a screening tool. By pooling data including the previous series and our current series, the cumulative frequency of the 16p13.3 microdeletion is 11.9% (19 in 159). This frequency of approximately 12% deleted patients appears more accurate than the 25% previously reported. Molecular investigations of CBP are in process in our series to clarify the cause of RTS.

FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy

“…By pooling data from this series and previous studies the cumulative frequency of the 16p13.3 microdeletions is 11% (24 of 219). 1,[3][4][5][6][7] Most previous FISH studies of RTS used only one probe (RT1). 1,3,4,6,7 Our use of different CBP probes in this study did not increase the frequency of detected deletions because all deletions found included RT100 which is very similar to RT1.…”

“…1,[3][4][5][6][7] Most previous FISH studies of RTS used only one probe (RT1). 1,3,4,6,7 Our use of different CBP probes in this study did not increase the frequency of detected deletions because all deletions found included RT100 which is very similar to RT1. 12 For future FISH studies we would recommend using several cosmids for the CBP gene, eg RT100 (exons 14-31), RT191 (exons 3-13) and possibly 420F6 (exon 2) or 304A10 (exon 1), as well as a panel of closely flanking probes (preferably cosmids) to enable the detection of partial deletions of the gene and accurately determine the extent of the A previous study demonstrated by flanking markers that all six deletions were located between cosmid 26 (PKD1/D16S125, telomeric) and cosmid N2 (D16S138, centromeric).…”

“…Except for ChromoprobeT16p each probe was used with 20 normal controls. No variability of hybridisation to normal chromosomes 16 14 we determined that RT100 (D16S237) spans 45 kb of the 3'-region of CBP, includes cosmid RT1 used elsewhere, 1,3,4,6,7 corresponds to AC004651 and the proximal segment of AC004760 and represents codons 822-2443 (exons 14-31). RT191 (AC004509) maps 10 kb centromeric to RT100 and spans 39595 bp including codons 267-821 (exons [3][4][5][6][7][8][9][10][11][12][13] and the CREB binding domain.…”

“…7 Deletions were observed in 6/24 (25%), 1/25 (4%), 2/16 (12.5%), 1/15 (6.7%), 7/64 (10.9%), and 3/30 (10%) of patients. 1,[3][4][5][6][7] Clinical differences between patients with and without deletions were reported to be minimal or absent, but the number of patients was too small to allow firm conclusions. 7,8 We report a prospective molecular cytogenetic study of 45 patients with RTS, four of whom were found to have a deletion.…”

“…1,[3][4][5][6][7] Clinical differences between patients with and without deletions were reported to be minimal or absent, but the number of patients was too small to allow firm conclusions. 7,8 We report a prospective molecular cytogenetic study of 45 patients with RTS, four of whom were found to have a deletion. Three patients with a deletion displayed traits or distinctive malformation patterns which are unusual in RTS, including death in infancy, polysplenia and the so-called hypoplastic left heart 'syndrome' (which sensu stricto represents a morphogenetic sequence).…”