MEF2C deletions and mutations versus duplications: a clinical comparison

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Genomic Imprinting

Background:

• 5q14.3 deletions encompassing the MEF2C gene are associated with severe developmental delay, intellectual disability, epilepsy, and specific facial features.
• MEF2C mutations are considered the primary cause of 5q14.3 deletion syndrome due to overlapping phenotypes.
• A single prior report of MEF2C duplication in intellectual disability lacked definitive clinical significance.

Observation:

• This study presents two new patients with 5q14.3 duplications that include the MEF2C gene.
• The observed phenotypes in these patients suggest a pathogenic role for MEF2C duplication.
• Other co-duplicated, brain-expressed genes may also influence the clinical presentation.

Findings:

• The clinical significance of MEF2C duplications is supported by the presented patient phenotypes.
• A distinct syndrome solely attributable to MEF2C duplication could not be identified.
• A comparative analysis of MEF2C deletion/mutation and duplication patient cohorts is provided.

Implications:

• MEF2C duplications are implicated in neurodevelopmental disorders, expanding the understanding of 5q14.3 deletion syndrome.
• Further research is needed to elucidate the precise contribution of MEF2C duplications and other co-duplicated genes.
• This study contributes to the diagnostic and etiological understanding of MEF2C-related genetic conditions.