Background: Rubinstein-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 (CREBBP or CBP) in 19p13.3. To date mutations in CREBBP have been reported in 56.6% of RSTS patients and an av. figure of 10% has ascribed to deletions. Methods: Our study is based on the mutation anal. of CREBBP in 31 Italian RSTS patients using segregation anal. of intragenic microsatellites, BAC FISH and direct sequencing of PCR and RT-PCR fragments. Results: We 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 missence change reported as recurrent mutation. Thirteen addnl. polymorphisms, three as of yet unreported, were also detected. Conclusion: A 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.

Rubinstein-Taybi syndrome : spectrum of CREBBP mutations in Italian patients / A. Bentivegna, D. Milani, C. Gervasini, P. Castronovo, F. Mottadelli, S. Manzini, P. Colapietro, L. Giordano, F. Atzeri, M.T. Divizia, M.L. Giovannucci Uzielli, G.i. Neri, M.F. Bedeschi, F. Faravelli, A. Selicorni, L. Larizza. - In: BMC MEDICAL GENETICS. - ISSN 1471-2350. - 7:7(2006 Oct), p. 77.77.

Rubinstein-Taybi syndrome : spectrum of CREBBP mutations in Italian patients.

C. Gervasini;P. Castronovo;F. Mottadelli;S. Manzini;P. Colapietro;L. Larizza
Ultimo
2006

Abstract

Background: Rubinstein-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 (CREBBP or CBP) in 19p13.3. To date mutations in CREBBP have been reported in 56.6% of RSTS patients and an av. figure of 10% has ascribed to deletions. Methods: Our study is based on the mutation anal. of CREBBP in 31 Italian RSTS patients using segregation anal. of intragenic microsatellites, BAC FISH and direct sequencing of PCR and RT-PCR fragments. Results: We 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 missence change reported as recurrent mutation. Thirteen addnl. polymorphisms, three as of yet unreported, were also detected. Conclusion: A 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.
Settore MED/03 - Genetica Medica
ott-2006
Article (author)
File in questo prodotto:
File Dimensione Formato  
BMC Medical Genetics 2006.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.39 MB
Formato Adobe PDF
1.39 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/42227
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 57
social impact