A novel PCDH19 mutation inherited from an unaffected mother

Area of Science:

• Genetics
• Neurology
• Epilepsy

Background:

• PCDH19 epilepsy, a rare X-linked disorder, typically affects females and is characterized by drug-resistant seizures.
• Genetic mutations in the PCDH19 gene are the underlying cause of this condition.

Observation:

• A 13-year-old girl presented with drug-resistant, fever-induced seizures starting at 5 months of age.
• She also exhibited worsening behavioral issues, including autistic and aggressive features.
• Her mother, who was asymptomatic, carried the same pathogenic PCDH19 mutation.

Findings:

• Molecular genetic testing identified a de novo duplication (c.2705dupA) in the PCDH19 gene (exon 5).
• This mutation was confirmed to be present in the unaffected mother, indicating carrier status.
• This case represents a rare instance of a pathogenic PCDH19 mutation inherited from a healthy heterozygous female carrier.

Implications:

• The findings underscore the significance of PCDH19 mutation testing in sporadic epilepsy cases with no family history.
• Testing should be considered in individuals presenting with characteristic features of X-linked epilepsy and mental retardation limited to females.
• This case expands the understanding of PCDH19 mutation inheritance patterns and diagnostic approaches.