SETD5 gene variant associated with mild intellectual disability - a case report

Area of Science:

• Genetics
• Neuroscience

Background:

• Intellectual disability (ID) is a heterogeneous condition with complex genetic underpinnings.
• Exome sequencing is a powerful tool for identifying molecular etiologies of previously undiagnosed diseases.

Observation:

• A 36-year-old male patient with mild intellectual disability underwent whole exome sequencing.
• Genetic analysis revealed a novel likely pathogenic frameshift insertion (c.3848_3849insC) in the SETD5 gene on chromosome 3.

Findings:

• The identified SETD5 variant is predicted to cause a loss-of-function mutation.
• Loss-of-function mutations in SETD5 are associated with intellectual disability and 3p25.3 microdeletion phenotypes.
• The patient's mild phenotype may be attributed to partial SETD5 gene activity due to its specific localization.

Implications:

• This case expands the spectrum of SETD5-related disorders and highlights its role in intellectual disability.
• The findings underscore the utility of exome sequencing in diagnosing rare genetic conditions.
• Further research into SETD5 variants can improve diagnostic yield and inform genotype-phenotype correlations in intellectual disability.