Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients
| Autor: | Angelo Selicorni, Lidia Larizza, Cristina Gervasini, Francesca Atzeri, L. Giordano, Federica Mottadelli, Francesca Faravelli, Maria Teresa Divizia, Paola Castronovo, Stefano Manzini, Patrizia Colapietro, Donatella Milani, Maria Francesca Bedeschi, Giovanni Neri, Angela Bentivegna, Maria L Giovannucci Uzielli |
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| Přispěvatelé: | Bentivegna, A, Milani, D, Gervasini, C, Castronovo, P, Mottadelli, F, Manzini, S, Colapietro, P, Giordano, L, Atzeri, F, Divizia, M, Uzielli, M, Neri, G, Bedeschi, M, Faravelli, F, Selicorni, A, Larizza, L |
| Jazyk: | angličtina |
| Předmět: |
Adult
Male lcsh:Internal medicine MED/03 - GENETICA MEDICA Adolescent lcsh:QH426-470 DNA Mutational Analysis Molecular Sequence Data Nuclear Localization Signals medicine.disease_cause Frameshift mutation medicine Genetics Missense mutation Humans Point Mutation Genetics(clinical) Amino Acid Sequence CREB-binding protein Child lcsh:RC31-1245 Genetics (clinical) Sequence Deletion Rubinstein-Taybi Syndrome Mutation Rubinstein–Taybi syndrome biology Point mutation medicine.disease Molecular biology CREB-Binding Protein Pedigree lcsh:Genetics Italy Rubinstein–Taybi syndrome CREB binding protein Child Preschool biology.protein Mutation testing Female Sequence Alignment Congenital disorder Research Article |
| Zdroj: | BMC Medical Genetics, Vol 7, Iss 1, p 77 (2006) BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/1471-2350-7-77 |
| Popis: | BackgroundRubinstein-Taybi Syndrome (RSTS, MIM 180849) is a rare congenital disorder characterized by mental and growth retardation, broad and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms and increased risk of tumors. RSTS is caused by chromosomal rearrangements and point mutations in one copy of the CREB-binding protein gene (CREBBPorCBP) in 16p13.3. To date mutations inCREBBPhave been reported in 56.6% of RSTS patients and an average figure of 10% has ascribed to deletions.MethodsOur study is based on the mutation analysis ofCREBBPin 31 Italian RSTS patients using segregation analysis of intragenic microsatellites, BAC FISH and direct sequencing of PCR and RT-PCR fragments.ResultsWe identified a total of five deletions, two of the entire gene and three, all in a mosaic condition, involving either the 5' or the 3' region. By direct sequencing a total of 14 de novo mutations were identified: 10 truncating (5 frameshift and 5 nonsense), one splice site, and three novel missense mutations. Two of the latter affect the HAT domain, while one maps within the conserved nuclear receptor binding of (aa 1–170) and will probably destroy a Nuclear Localization Signal. Identification of the p.Asn1978Ser in the healthy mother of a patient also carrying a de novo frameshift mutation, questions the pathogenetic significance of the missense change reported as recurrent mutation. Thirteen additional polymorphisms, three as of yet unreported, were also detected.ConclusionA high detection rate (61.3%) of mutations is confirmed by this Italian study which also attests one of the highest microdeletion rate (16%) documented so far. |
| Databáze: | OpenAIRE |
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