A New EP300 -Related Syndrome With Prominent Developmental and Immune Phenotypes.

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Rubinstein-Taybi syndrome (RTS) is a genetic disorder linked to pathogenic variants in CREBBP and EP300, affecting chromatin remodeling and gene transcription.
• RTS typically presents with intellectual disability, distinctive facial features, and organ malformations.
• Recent studies suggest allelic disorders with variants in specific EP300 regions, presenting with neurodevelopmental issues but lacking typical RTS features.

Purpose of the Study:

• To investigate a family with mild dysmorphisms, recurrent respiratory infections, and speech delay.
• To identify the genetic cause of the observed phenotype.
• To explore the phenotypic spectrum associated with EP300 variants.

Main Methods:

• Whole exome sequencing was performed to identify genetic variants.
• Methylation testing was conducted to analyze epigenetic patterns.
• Clinical data from the affected family was reviewed.

Main Results:

• A novel missense variant in exon 8 of EP300, within the KIX CBP coactivator domain, was identified in the affected family.
• Methylation testing revealed an abnormal pattern overlapping with both RTS and Cornelia de Lange syndromes.
• The identified variant was associated with mild dysmorphisms, recurrent respiratory infections, and speech delay, distinguishing it from typical RTS.

Conclusions:

• Missense variants in EP300 may lead to a distinct neurodevelopmental syndrome with a milder phenotype compared to classic RTS.
• The findings expand the known clinical spectrum of EP300-related disorders.
• Further research is needed to fully elucidate the genotype-phenotype correlations for EP300 variants.