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

Molecular Genetics & Genomic Medicine
Josephine WincentBritt-Marie Anderlid

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.

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Citations

Dec 15, 2016·BMC Medical Genetics·María LópezElena Domínguez-Garrido
Jan 24, 2018·American Journal of Medical Genetics. Part a·Max V BootDaphne de Jong
Oct 26, 2018·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·V TamD Meyre
Oct 1, 2019·Molecular Genetics & Genomic Medicine·Virginia Pérez-GrijalbaElena Domínguez-Garrido
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Jul 3, 2021·Genes·Julien Van GilsDidier Lacombe

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Methods Mentioned

BETA
Feature Extraction
PCR

Software Mentioned

ABI SEQSCAPE
PolyPhen
Cytosure Interpret
Alamut
Feature Extraction

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