Abstract / Summary
Background: The Embryonic Ectoderm Development (EED) gene encodes a core component of the Polycomb Repressive Complex 2 (PRC2), which regulates chromatin structure and plays a key role in embryonic development and cell differentiation. Pathogenic variants in EED are associated with overgrowth-intellectual disability syndrome (Cohen-Gibson syndrome, OMIM #617561), though reported cases are rare and typically involve heterozygous germline variants. This study presents an individual with confirmed postzygotic mosaicism in EED, contributing to diagnostic complexity.
Methods: A 12-year-old girl with tall stature, dysmorphic features, developmental delay, and congenital anomalies underwent clinical and genetic evaluation. Exome sequencing and targeted deep sequencing were used to identify and validate the genetic variant across multiple tissues.
Results: A likely pathogenic mosaic EED variant c.1091G > T; p.(Trp364Leu) was identified in the patient with a 31% variant allele fraction in peripheral blood. Deep sequencing confirmed the variant and its de novo origin in the parents' samples. Mosaicism was also detected in two independently collected buccal mucosa samples (dry swab and buccal swab collection kit; 11% and 17%) and in saliva (30%), indicating somatic mosaicism in multiple tissues. DNA methylation profiling revealed a high-confidence epigenetic signature consistent with a PRC2 complex-associated disorder, further supporting the likely pathogenic classification of the identified variant.
Conclusion: This case broadens the molecular understanding of EED-related disorders and highlights the clinical significance of mosaicism. Deep sequencing and multi-tissue analysis are crucial for accurate diagnosis, management, and genetic counseling in overgrowth syndromes.