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. 2025 Aug;197(8):e64050.
doi: 10.1002/ajmg.a.64050. Epub 2025 Apr 1.

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

Devi Priyanka Maripuri  1   2 , Jessica Gold  3 , Nina Gold  4   5 , Alanna Strong  1   2   6
Affiliations

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

Devi Priyanka Maripuri et al. Am J Med Genet A. 2025 Aug.

Abstract

Rubinstein Taybi syndrome (RTS) is a disorder of chromatin remodeling and transcriptional regulation caused by heterozygous pathogenic variants in CREBBP and EP300. RTS is characterized by a distinct facial gestalt, intellectual disability, structural kidney and heart differences, feeding difficulties, and broad thumbs and great toes. Individuals with EP300 variants tend to have milder disease, but overall disease features are similar. Recently, a cohort of individuals with heterozygous variants in exons 30-31 of CREBBP and homologous regions in EP300 was described. Affected individuals presented with global developmental delay, autism, feeding difficulties, vision and hearing impairment, and microcephaly, but did not share the typical RTS facial gestalt or organ malformations, suggesting an allelic disorder. Here we present a family with mild dysmorphisms, recurrent respiratory infections, and speech delay found by exome sequencing to have a missense variant in exon 8 of EP300 in the KIX CBP coactivator domain. Follow-up methylation testing revealed an abnormal methylation pattern overlapping with both RTS and Cornelia de Lange syndromes. We propose that missense variants in EP300 may cause a distinct neurodevelopmental syndrome with a milder phenotype.

Keywords: EP300; Cornelia de Lange syndrome; Episignature; Rubinstein Taybi syndrome; methylation patterns.

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References

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