Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients, BMC Medical Genetics

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 16p13.3. To date mutations in CREBBP have been reported in 56.6% of RSTS patients and an average figure of 10% has ascribed to deletions. Methods Our study is based on the mutation analysis of CREBBP in 31 Italian RSTS patients using segregation analysis 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 missense change reported as recurrent mutation. Thirteen additional 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.

Ultra-Rare Syndromes: The Example of Rubinstein-Taybi Syndrome. - Abstract - Europe PMC

Transcriptome Analysis of iPSC-Derived Neurons from Rubinstein-Taybi Patients Reveals Deficits in Neuronal Differentiation

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Figure 2 from A case of Rubinstein-Taybi Syndrome with a CREB-binding protein gene mutation

Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients, BMC Medical Genetics

Characterization of 14 novel deletions underlying Rubinstein–Taybi syndrome: an update of the CREBBP deletion repertoire

Rubinstein–Taybi Syndrome in a Filipino Infant with a Novel CREBBP Gene Pathogenic Variant

Rubinstein-Taybi Syndrome and Epigenetic Alterations. - Abstract - Europe PMC

Rubinstein–Taybi syndrome: clinical and molecular overview, Expert Reviews in Molecular Medicine

A submicroscopic deletion involving part of the CREBBP gene detected by array-CGH in a patient with Rubinstein–Taybi syndrome - ScienceDirect

High frequency of copy number imbalances in Rubinstein–Taybi patients negative to CREBBP mutational analysis