title: Screening for partial deletions in the CREBBP gene in Rubinstein-Taybi syndrome patients using multiplex PCR/liquid chromatography.
abstract: Rubinstein-Taybi syndrome (RTS, MIM 180849) is a multiple malformation syndrome characterized by growth retardation, developmental delay, and dysmorphic features, including down-slanting palpebral fissures, a beaked nose, broad thumbs, and halluces. Mutations in the gene encoding the CREB-binding protein gene (CREBBP, also known as CBP) on chromosome 16p13.3 were identified in 1995. Recently, we developed a mutation analysis protocol using denaturing high-performance liquid chromatography (DHPLC) and identified heterozygous CREBBP mutations in 12 of 21 RTS patients. To test whether exonic deletions represent a common pathogenic mechanism, we assessed the copy number of all the coding exons using a recently developed method, the multiplex PCR/liquid chromatography assay (MP/LC). By using MP/LC, we performed screening for CREBBP exonic deletions among 25 RTS patients in whom no point mutations or small insertions/deletions were identified by DHPLC screening. We identified four classic RTS patients with deletions encompassing multiple exons (14-16, 5-31, 1-16, and 4-26). We conclude that large deletions including several exons are a relatively frequent cause of RTS, and that MP/LC is an effective method for detecting these deletions.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Udaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yoshida
authors.forename: Masato
authors.initials: M
authors.lastname: Tsukahara
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Torii
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Masuno
authors.forename: Noboru
authors.initials: N
authors.lastname: Hosokai
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
mesh_terms: D050882:CREB-Binding Protein / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005820:Genetic Testing / Q000379:methods*; D020180:Heteroduplex Analysis; D006801:Humans; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D012415:Rubinstein-Taybi Syndrome / Q000175:diagnosis* / Q000235:genetics
chemical_list: D050882:CREB-Binding Protein; C494363:CREBBP protein, human