Male patients affected by mosaic PCDH19 mutations: five new cases

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Pathogenic variants in the PCDH19 gene are linked to epilepsy, intellectual disability (ID), and behavioral issues.
• The PCDH19-related disorder primarily affects heterozygous females and mosaic males due to a cellular interference mechanism.
• Previously, only four affected mosaic males with PCDH19 gene variants had been documented.

Purpose of the Study:

• To report on five additional mosaic male patients with PCDH19 gene variants.
• To further characterize the clinical phenotype of PCDH19-related disorders in males.
• To compare the male phenotype with the established female phenotype.

Main Methods:

• Genetic analysis using custom-targeted next-generation sequencing gene panels for epilepsy genes.
• Clinical data collection from medical records of affected individuals.
• Identification of likely pathogenic variants in the PCDH19 gene in mosaic males.

Main Results:

• Five mosaic male patients with likely pathogenic PCDH19 variants were identified.
• Three patients presented with epilepsy, developmental delay, and behavioral problems.
• Clinical features in these males largely mirrored the known female phenotype, including early-onset seizures and fever sensitivity.

Conclusions:

• This study expands the cohort of known mosaic males with PCDH19 gene variants.
• The findings reinforce the phenotypic similarity between males and females with PCDH19-related disorders.
• The results provide insights into the long-term clinical course of the disorder in males up to adolescence.