Partial deletion of DEPDC5 in a child with focal epilepsy

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Focal epilepsy is a neurological disorder characterized by abnormal electrical activity in one hemisphere of the brain.
• Mutations in the DEPDC5 gene are known to cause inherited focal epileptic syndromes.
• The DEP domain-containing protein 5 (DEPDC5) plays a crucial role in cellular processes relevant to neuronal function.

Purpose of the Study:

• To investigate the genetic basis of focal epilepsy in a child with borderline intelligence and normal brain MRI.
• To determine the role of DEPDC5 gene mutations in sporadic cases of focal idiopathic epilepsy.
• To elucidate the functional impact of a partial DEPDC5 gene deletion.

Main Methods:

• Polysomnographic electroencephalogram (EEG) recording to characterize seizure activity.
• Array comparative genomic hybridization (aCGH) to detect genomic deletions.
• Analysis of DEPDC5 gene transcripts and protein domains.

Main Results:

• The patient presented with focal epilepsy and asynchronous central spikes on EEG.
• A 32-kb partial deletion of the DEPDC5 gene was identified.
• The deletion affects all alternatively spliced isoforms, resulting in a DEPDC5 protein lacking the entire DEP domain.
• The deletion was confirmed to be present in the patient but parental origin could not be fully ascertained due to assisted reproductive technology.

Conclusions:

• Partial deletion of the DEPDC5 gene can be sufficient to cause focal epilepsy.
• The DEP domain of DEPDC5 is critical for its function in preventing epilepsy.
• This study expands the known genetic spectrum of DEPDC5 mutations to include sporadic focal idiopathic epilepsy.
• Partial DEPDC5 deletions represent a rare but significant cause of focal epilepsy.