From Whole Gene Deletion to Point Mutations ofEP300-Positive Rubinstein-Taybi Patients: New Insights into the Mutational Spectrum and Peculiar Clinical Hallmarks
| Autor: | Federica Tamburrino, Milena Crippa, Tommaso Pippucci, Gloria Negri, Emanuela Scarano, Daniela Rusconi, Palma Finelli, Anita Wischmeijer, Lidia Larizza, Laura Mazzanti, Maria Teresa Bonati, Manuela Priolo, Cristina Gervasini, Donatella Milani, Pamela Magini, Patrizia Colapietro |
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| Přispěvatelé: | Negri, Gloria, Magini, Pamela, Milani, Donatella, Colapietro, Patrizia, Rusconi, Daniela, Scarano, Emanuela, Bonati, Maria Teresa, Priolo, Manuela, Crippa, Milena, Mazzanti, Laura, Wischmeijer, Anita, Tamburrino, Federica, Pippucci, Tommaso, Finelli, Palma, Larizza, Lidia, Gervasini, Cristina |
| Rok vydání: | 2015 |
| Předmět: |
Male
0301 basic medicine Adolescent Gene Expression genotype-phenotype correlation Biology Bioinformatics medicine.disease_cause Young Adult 03 medical and health sciences Exon Neurodevelopmental disorder Gene duplication Genetics medicine Humans deletion Child EP300 Genetic Association Studies In Situ Hybridization Fluorescence Rubinstein-Taybi syndrome Genetics (clinical) Mutation Rubinstein–Taybi syndrome Genome Human Point mutation Genetic Variation Sequence Analysis DNA medicine.disease CREB-Binding Protein Phenotype RSTS 030104 developmental biology Female E1A-Associated p300 Protein |
| Zdroj: | Human Mutation. 37:175-183 |
| ISSN: | 1059-7794 |
| Popis: | Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by growth deficiency, skeletal abnormalities, dysmorphic features, and intellectual disability. Causative mutations in CREBBP and EP300 genes have been identified in ∼55% and ∼8% of affected individuals. To date, only 28 EP300 alterations in 29 RSTS clinically described patients have been reported. EP300 analysis of 22 CREBBP-negative RSTS patients from our cohort led us to identify six novel mutations: a 376-kb deletion depleting EP300 gene; an exons 17-19 deletion (c.(3141+1_3142-1)_(3590+1_3591-1)del/p.(Ile1047Serfs*30)); two stop mutations, (c.3829A>T/p.(Lys1277*) and c.4585C>T/p.(Arg1529*)); a splicing mutation (c.1878-12A>G/p.(Ala627Glnfs*11)), and a duplication (c.4640dupA/p.(Asn1547Lysfs*3)). All EP300-mutated individuals show a mild RSTS phenotype and peculiar findings including maternal gestosis, skin manifestation, especially nevi or keloids, back malformations, and a behavior predisposing to anxiety. Furthermore, the patient carrying the complete EP300 deletion does not show a markedly severe clinical picture, even if a more composite phenotype was noticed. By characterizing six novel EP300-mutated patients, this study provides further insights into the EP300-specific clinical presentation and expands the mutational repertoire including the first case of a whole gene deletion. These new data will enhance EP300-mutated cases identification highlighting distinctive features and will improve the clinical practice allowing a better genotype-phenotype correlation. |
| Databáze: | OpenAIRE |
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