Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum, BMC Medical Genetics
Por um escritor misterioso
Descrição
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.
Rubinstein-Taybi Syndrome - an overview
Genetic heterogeneity in Rubinstein–Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300
Hyperinsulinism in an individual with an EP300 variant of Rubinstein-Taybi syndrome. - Abstract - Europe PMC
Genes, Free Full-Text
Identification of de novo EP300 and PLAU variants in a patient with Rubinstein–Taybi syndrome-related arterial vasculopathy and skeletal anomaly
Frontiers Genetic Diagnosis of Rubinstein–Taybi Syndrome With Multiplex Ligation-Dependent Probe Amplification (MLPA) and Whole-Exome Sequencing (WES): Case Series With a Novel CREBBP Variant
High frequency of copy number imbalances in Rubinstein–Taybi patients negative to CREBBP mutational analysis
De novo variation in EP300 gene cause Rubinstein-Taybi syndrome 2 in a Chinese family with severe early-onset high myopia, BMC Medical Genomics
Images showing classical RSTS features of patient including thickened
Distribution of CREBBP domains and mutations in our patient (in green)
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