A novel mutation in EED associated with overgrowth

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Weaver syndrome is a genetic disorder characterized by overgrowth, typically caused by mutations in the EZH2 gene.
• The Polycomb Repressive Complex 2 (PRC2) is crucial for gene silencing and development, involving proteins like EZH2 and EED.
• Identifying the genetic basis of rare overgrowth syndromes is essential for diagnosis and understanding developmental pathways.

Observation:

• A patient with clinical suspicion of Weaver syndrome was investigated.
• Mutations in EZH2 and NSD1 were excluded as the cause of the patient's condition.
• A previously undescribed de novo mutation in the EED gene was identified.

Findings:

• The identified EED mutation is likely pathogenic, causing a Weaver-like overgrowth syndrome.
• This represents the first report of overgrowth phenotypes associated with a constitutional mutation in human EED.
• The study highlights the role of EED in human overgrowth disorders, similar to EZH2.

Implications:

• This discovery expands the spectrum of genetic causes for Weaver-like overgrowth syndromes.
• It provides new insights into the function of the EED gene and PRC2 in human development.
• The findings may aid in the clinical diagnosis of overgrowth syndromes and inform genetic counseling.