Doublecortin Mutation in an Adolescent Male

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Doublecortin (DCX) protein is crucial for neuronal migration during fetal development.
• Mutations in the DCX gene lead to lissencephaly (smooth brain), characterized by pachygyria or agyria.
• X-linked DCX mutations present differently in males (lissencephaly) and females (subcortical heterotopia).

Observation:

• A 13-year-old male presented with new-onset seizures, a history of developmental delay, and autism spectrum disorder features.
• Brain MRI revealed frontal and temporal lobe pachygyria, consistent with X-linked lissencephaly sequence.
• Extensive genetic testing identified a de novo mosaic mutation (c.30-31 deletion) in the DCX gene via whole-exome sequencing.

Findings:

• The patient's presentation is atypical, lacking infantile seizures, severe intellectual disability, orthopedic complications, and postnatal microcephaly common in DCX mutations.
• This case demonstrates a unique mosaic DCX mutation with a distinct clinical phenotype.
• Whole-exome sequencing proved effective in diagnosing rare genetic variants like mosaic mutations.

Implications:

• This case expands the understanding of genotype-phenotype correlations in DCX-related lissencephaly.
• Highlights the importance of considering mosaic mutations in genetic diagnostics, especially with atypical presentations.
• Suggests potential for milder phenotypes in individuals with specific mosaic DCX mutations, warranting further investigation.