Identification of PCDH19 Gene Mutations/Deletions in Patients with Early Onset Epilepsy
Semra Gursoy1, Esra Ataman2, Bahar Toklu Baysal3
1Department of Pediatric Genetics, Dr. Behcet Uz Children's Hospital, Izmir, Turkey.
Insights
Mutations and deletions in the PCDH19 gene are linked to epilepsy in females. Analyzing PCDH19 deletions and mutations improves molecular diagnosis for early-onset epilepsy and intellectual disability.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- The PCDH19 gene encodes protocadherin 19, implicated in epilepsy and intellectual disability, predominantly in females.
- Clinical presentations are diverse, featuring early-onset seizures, fever-sensitive seizures, and clustered seizure episodes, with a distinct X-linked inheritance pattern.
Purpose of the Study:
- To investigate PCDH19 mutations and deletions in patients diagnosed with epilepsy.
- To characterize the clinical and molecular features associated with PCDH19 alterations.
Main Methods:
- Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) were employed to analyze the PCDH19 gene in 35 Turkish female patients with early-onset epilepsy.
- Array comparative genomic hybridization (aCGH) was utilized for patients exhibiting whole gene deletions.
Main Results:
- Two distinct heterozygous mutations in exon 1 of PCDH19 were identified in 2 unrelated probands (5.7%).
- Whole gene deletions were detected in dizygotic twin sisters (5.7%), inherited from their unaffected father, with differing clinical severity.
- The second twin presented with more severe symptoms, including autistic features, behavioral issues, and mild-moderate intellectual disability.
Conclusions:
- PCDH19 is a significant causative gene in epilepsy patients, necessitating further research for comprehensive phenotype-genotype correlation.
- Integrating deletion/duplication analysis alongside gene sequencing enhances molecular diagnostic capabilities for patients presenting with relevant clinical findings.
Background And Aims:
PCDH19 gene, which encodes protocadherin 19, is associated with epilepsy and intellectual disability, mainly in affected females. The clinical manifestations are heterogeneous and the main features include early onset seizure, generalized or focal seizures sensitive to fever, and brief seizures occurring in clusters. The disorders exhibit a unique and unusual X-linked pattern of expression. We aimed to investigate PCDH19 mutations/deletions in patients with epilepsy and describe the clinical/molecular features.
Methods:
PCDH19 gene was analyzed in 35 Turkish female patients from 34 families with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification analysis. Additionally, array comparative genomic hybridization analysis was performed in patients with whole gene deletion.
Results:
We identified 2 different heterozygous mutations in 2 unrelated probands (5. 7%) which were located in exon 1. Additionally, whole gene deletions were detected in dizygotic twin girls (5. 7%), who had distinct clinical features and the deletion was inherited from the unaffected father. The second twin suffered more severe clinical manifestations including autistic features, behavioral problems, mild-moderate mental retardation and seizures, which were under control with multidrug regimen when compared with the first twin.
Conclusion:
PCDH19 is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.
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