Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• SETD2 gene mutations are implicated in neurodevelopmental disorders like autism spectrum disorder (ASD).
• Comprehensive genotype-phenotype correlations for SETD2 variants are currently limited.
• Previous studies identified SETD2 variants through large-cohort sequencing.

Observation:

• Two novel de novo SETD2 variants (splicing and missense) were identified in individuals diagnosed with ASD.
• A systematic review and manual curation of 17 reported de novo SETD2 variants were performed.
• Common phenotypes associated with de novo SETD2 variants include developmental delays, intellectual disability, macrocephaly, ASD, overgrowth, and recurrent otitis media.

Findings:

• Novel de novo SETD2 mutations were discovered through targeted sequencing.
• A comprehensive review of existing literature identified 17 individuals with de novo SETD2 variants.
• The study details a relatively consistent phenotype spectrum for SETD2-related neurodevelopmental disorders.

Implications:

• This research expands the understanding of SETD2 mutations in neurodevelopmental disorders.
• The identified phenotype spectrum can assist in disease classification and clinical diagnosis.
• Further research into SETD2's role in epigenetic regulation and development is warranted.