CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein–Taybi syndrome

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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 inEP300 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.

Keywords:
CREBBP, delayed emergence after anesthesia, EP300, preeclampsia, Rubinstein-Taybi syndrome

Autoři: Josephine Wincent ^1,*; Aron Luthman ¹; Martine Van Belzen ²; Christian Van Der Lans ²; Johanna Albert ³; Ann Nordgren ^1,4; †; Britt-Marie Anderlid ^1,4; †
Působiště autorů: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, CMM L8:0 , Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden ¹; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands ²; Division of Surgery, Department of Clinical Science, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden ³; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden †These authors contributed equally to this work. ⁴
Vyšlo v časopise: Molecular Genetics & Genomic Medicine 2015; Early View(Early View)
Kategorie: Original Research
prolekare.web.journal.doi_sk: https://doi.org/10.1002/mgg3.177

© 2015 University of Pretoria. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Souhrn

Keywords:
CREBBP, delayed emergence after anesthesia, EP300, preeclampsia, Rubinstein-Taybi syndrome

Zdroje

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