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Rubinstein-Taybi syndrome (RTS, MIM 180849) occurs in 1/125 000 births and is characterised by growth retardation and psychomotor developmental delay, broad and duplicated distal phalanges of the thumbs and halluces, typical facial dysmorphism, and an increased risk of neoplasia.1 RTS has been shown to be associated with chromosomal rearrangements in cytogenetic band 16p13.3,2–4 all involving the CREB binding protein gene, officially named CREBBP by the HUGO Nomenclature Committee, but generally referred to by its shorter acronym CBP.5CBP is a transcriptional coactivator involved in different signal transduction pathways, thereby regulating the expression of many genes and playing an important role in the regulation of cell growth, cellular differentiation, and tumour suppression.6,7 To date, all studies concerning CBP in RTS have used FISH analysis with cosmids from the CBP region or the search for mutations at the molecular level using the protein truncation test.8,9 Taken together, these studies showed that translocations and inversions form the minority of CBP mutations in RTS, microdeletions account for only 10% of RTS cases, and PTT studies showed 10% truncating mutations. The structure of the CBP gene was recently described.8CBP spans about 150 kb with 31 exons and its cDNA is 9 kb in length.
We report here the use of different molecular techniques to analyse the CBP gene in a cohort of 60 RTS patients. These include cDNA probes to search for gross rearrangements by Southern blot analysis and to identify CBP mRNA of abnormal sizes on northern blots, intragenic microsatellite markers to look for intragenic deletions, as well as a complete series of primers to PCR amplify each of the 31 exons of the gene for mutation searching by direct sequencing. We have analysed 60 patients using these various techniques and identified 27 …