Genetic Characterization of Rubinstein-Taybi Syndrome

Rubinstein-Taybi syndrome is a rare autosomal dominant disorder marked by intellectual disability, distinctive facial dysmorphism and broad distal phalanges. It is primarily caused by heterozygous pathogenic variants in CREBBP (approximately 55% of cases) and EP300 (around 8%), which encode the histone acetyltransferases CBP and p300. These enzymes regulate chromatin structure and transcription by acetylating lysine residues on histone and non-histone proteins. Genetic alterations include point mutations, small insertions or deletions and larger copy-number changes that disrupt critical domains responsible for acetyltransferase activity and protein interactions. Clinical heterogeneity complicates genotype–phenotype correlations, but advances in high-throughput sequencing and epigenomic profiling have enabled the identification of domain-specific DNA methylation episignatures. Functional studies using patient‐derived models have further elucidated how CBP/p300 deficiency impairs neuronal differentiation, synapse formation and neural migration. Integrating multi-omic data aims to improve diagnostic accuracy, enable prognostic markers and inform the development of targeted, epigenetic‐based therapies.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Genetic Characterization of Rubinstein-Taybi Syndrome publication trend

The graph below shows the total number of articles in genetic characterization of rubinstein-taybi syndrome across all publications each year (not limited to Nature Index journals).

Technical terms

CREBBP: Gene encoding CREB-binding protein, a histone acetyltransferase that coactivates transcription by modifying chromatin.

EP300: Gene encoding p300, a paralogue of CBP with lysine acetyltransferase activity essential for gene regulation during development.

Histone acetyltransferase (HAT): Enzyme that transfers acetyl groups to lysine residues on histone proteins, loosening chromatin and promoting transcription.

Multiplex ligation-dependent probe amplification (MLPA): Molecular method to detect copy-number variations in selected genomic regions.

Whole-exome sequencing (WES): High-throughput sequencing technique targeting all protein-coding regions of the genome to identify genetic variants.

DNA methylation episignature: Disease-specific pattern of DNA methylation used as a biomarker to stratify molecular subtypes and support diagnosis.

References

1. Rubinstein-Taybi Syndrome: A Model of Epigenetic Disorder. Genes (2021).
2. Transcriptome Analysis of iPSC-Derived Neurons from Rubinstein-Taybi Patients Reveals Deficits in Neuronal Differentiation. Molecular Neurobiology (2020).
3. Genetic Diagnosis of Rubinstein–Taybi Syndrome With Multiplex Ligation-Dependent Probe Amplification (MLPA) and Whole-Exome Sequencing (WES): Case Series With a Novel CREBBP Variant. Frontiers in Genetics (2022).