Submicroscopic deletions at 16p13.3 in Rubinstein-Taybi syndrome: frequency and clinical manifestations in a North American population.

Abstract

Methods ASCERTAINMENTSixty-four patients with the diagnosis of RTS were ascertained through the Rubinstein-Taybi Parent Group (47 (73%)) and referrals from other genetic centres (17 (27%)). Clinical data, photographs, and medical records were collected on each patient to confirm the diagnosis of RTS. Thirty-nine specific traits, including growth parameters, were assessed for each patient. Since RTS is a short stature syndrome, microcephaly in this context was used as 1 SD below the 50th centile height age to assess true microcephaly in relation to body size and not small head size resulting from overall growth deficiency. Clinical assessment was made before knowledge of deletion status to minimise potential bias and to test the hypothesis that there are clinically distinguishable differences between deletion and non-deletion patients. CYTOGENETIC STUDIESPeripheral lymphocytes were cultured for 72 hours using conventional methods. Karyotyping with GTG banding was performed at the 550 to 750 band level. A minimum offive metaphase preparations were examined from each patient. MOLECULAR STUDIESThe RT1 cosmid (D16S237), approximately 56 kb in size, was obtained in an E coli MC 1046 host. The presence of the probe was confirmed by digestion with EcoRI, which yielded a specific 5.2 kb fragment. The cosmid was

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).…”

“…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. 12,14 The 36-kb clone RT203 maps centromeric to RT191 and represents a segment of the large intron between exon 2 (codons 29-266, on AC005564) and exon 3 (codons 267-325, on AC004509).…”

“…Britain, 4 the USA, 5,6 and France. 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.…”

“…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.…”