title: CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome.
abstract: Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant congenital disorder characterized by distinctive facial features, broad thumbs and halluces, growth retardation, and a variable degree of cognitive impairment. CREBBP is the major causative gene and mutations in EP300 are the cause of RTS in a minority of patients. In this study, 17 patients with a clinical diagnosis of RTS were investigated with direct sequencing, MLPA, and array-CGH in search for mutations in these two genes. Eleven patients (64.7%) had disease-causing point mutations or a deletion in CREBBP and in one patient (5.9%) a causal de novo frameshift mutation in EP300 was identified. This patient had broad thumbs, mild intellectual disability, and autism. In addition, an inherited missense mutation of uncertain clinical significance was identified in EP300 in one patient and his healthy father, and three patients had intronic nucleotide changes of uncertain clinical significance in CREBBP. Snoring and sleep apnea were common in both groups and four of the patients' mothers had preeclampsia during pregnancy. Importantly, difficulties associated with anesthesia were frequently reported and included delayed or complicated emergency in 53.3% of patients.
authors.affiliation: Department of Molecular Medicine and Surgery Center for Molecular Medicine CMM L8:02 Karolinska Institutet Karolinska University Hospital Stockholm Sweden.
authors.forename: Josephine
authors.initials: J
authors.lastname: Wincent
authors.affiliation: Department of Molecular Medicine and Surgery Center for Molecular Medicine CMM L8:02 Karolinska Institutet Karolinska University Hospital Stockholm Sweden.
authors.forename: Aron
authors.initials: A
authors.lastname: Luthman
authors.affiliation: Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: van Belzen
authors.affiliation: Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: van der Lans
authors.affiliation: Division of Surgery Department of Clinical Science Karolinska Institutet Danderyd Hospital Stockholm Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Albert
authors.affiliation: Department of Molecular Medicine and SurgeryCenter for Molecular MedicineCMM L8:02Karolinska InstitutetKarolinska University HospitalStockholmSweden; Department of Clinical GeneticsKarolinska University HospitalStockholmSweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.affiliation: Department of Molecular Medicine and SurgeryCenter for Molecular MedicineCMM L8:02Karolinska InstitutetKarolinska University HospitalStockholmSweden; Department of Clinical GeneticsKarolinska University HospitalStockholmSweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Anderlid
keywords: CREBBP; EP300; Rubinstein‐Taybi syndrome; delayed emergence after anesthesia; preeclampsia