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.

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

Rubinstein-Taybi syndrome: MedlinePlus Genetics

PDF) Rubinstein-Taybi Syndrome: Spectrum of CREBBP mutations in Italian patients

Rubinstein–Taybi syndrome - Wikipedia

PDF) A case of Rubinstein-Taybi Syndrome with a CREBbinding protein gene mutation

A novel CREBBP mutation and its phenotype in a case of Rubinstein–Taybi syndrome, BMC Medical Genomics

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

iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability - ScienceDirect

PDF) New insights into genetic variant spectrum and genotype–phenotype correlations of Rubinstein‐Taybi syndrome in 39 CREBBP‐ positive patients

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein– Taybi and Filippi syndromes