CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein–Taybi syndrome. Issue 1 (22nd September 2015)

• Record Type: Journal Article
• Authors: Wincent, Josephine; Luthman, Aron; van Belzen, Martine; van der Lans, Christian; Albert, Johanna; Nordgren, Ann; Anderlid, Britt‐Marie
• Is Part Of: Molecular genetics & genomic medicine. Volume 4:Issue 1(2016)
• Page Start: 39
• Page End: 45
• Publication Date: 2015-09-22
• Subjects: CREBBP -- delayed emergence after anesthesia -- EP300 -- preeclampsia -- Rubinstein‐Taybi syndrome; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.177
• Languages: English
• ISSNs: 2324-9269

Abstract

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. Abstract : In this study, we report the mutation spectrum in CREBBP and EP300 among 17 Swedish patients with a clinical diagnosis of Rubinstein–Taybi syndrome, including a novel pathogenic EP300 mutation and intronic CREBBP alterations of uncertain clinical significance, together with detailed clinical phenotypes. 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 emergence in 53.3% of patients.