Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum, BMC Medical Genetics

Background Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50–60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present the clinical and molecular characterization of a cohort of RSTS patients carrying EP300 mutations. Methods Patients were selected from a cohort of 72 individuals suspected of RSTS after being negative in CREBBP study. MLPA and panel-based NGS EP300 were performed. Results Eight patients were found to carry EP300 mutations. Phenotypic characteristics included: intellectual disability (generally mild), postnatal growth retardation, infant feeding problems, psychomotor and language delay and typical facial dysmorphisms (microcephaly, downslanting palpebral fissures, columella below the alae nasi, and prominent nose). Broad thumbs and/or halluces were common, but angulated thumbs were only found in two patients. We identified across the gene novel mutations, including large deletion, frameshift mutations, nonsense, missense and splicing alterations, confirming de novo origin in all but one (the mother, possibly underdiagnosed, has short and broad thumbs and had learning difficulties). Conclusions The clinical evaluation of our patients corroborates that clinical features in EP300 are less marked than in CREBBP patients although it is difficult to establish a genotype-phenotype correlation although. It is remarkable that these findings are observed in a RSTS-diagnosed cohort; some patients harbouring EP300 mutations could present a different phenotype. Broadening the knowledge about EP300-RSTS phenotype may contribute to improve the management of patients and the counselling to the families.

De novo variation in EP300 gene cause Rubinstein-Taybi syndrome 2 in a Chinese family with severe early-onset high myopia, BMC Medical Genomics

Identification of de novo EP300 and PLAU variants in a patient with Rubinstein–Taybi syndrome-related arterial vasculopathy and skeletal anomaly

BMC Medical Genetics 1/2018

Skeletal findings of patients carrying mutations of the EP300 gene

Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein –Taybi syndrome detected by aCGH

A case with Rubinstein-Taybi syndrome: A novel frameshift mutation in the CREBBP gene.

Genes, Free Full-Text

PDF) Genetic and clinical heterogeneity in Korean patients with Rubinstein– Taybi syndrome

Rubinstein-Taybi Syndrome 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein–Taybi syndrome - Menke - 2018 - American Journal of Medical Genetics Part A - Wiley Online Library

Case report: a Chinese girl like atypical Rubinstein–Taybi syndrome caused by a novel heterozygous mutation of the EP300 gene, BMC Medical Genomics