Related Experiment Video

Updated: Jan 21, 2026

Calcium Imaging of Cortical Neurons using Fura-2 AM
12:15

Calcium Imaging of Cortical Neurons using Fura-2 AM

Published on: January 19, 2009

62.9K

Second-hit DEPDC5 mutation is limited to dysmorphic neurons in cortical dysplasia type IIA

Wei Shern Lee1,2, Sarah E M Stephenson1,2, Katherine B Howell1,2,3,4

  • 1Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Annals of Clinical and Translational Neurology
|July 30, 2019
PubMed

Insights

Focal cortical dysplasia (FCD), a cause of drug-resistant epilepsy, may involve a two-hit genetic model. A second DEPDC5 variant in dysmorphic neurons correlated with epilepsy severity, supporting this hypothesis.

Area of Science:

  • Neuroscience
  • Genetics
  • Epilepsy Research

Background:

  • Focal cortical dysplasia (FCD) is a leading cause of intractable epilepsy, often linked to genetic mutations within the mTOR signaling pathway.
  • The precise mechanism by which germline variants lead to focal brain lesions in FCD remains incompletely understood, with a "two-hit" germline-plus-somatic model being a prominent hypothesis.

Observation:

  • A study examined a male patient presenting with drug-resistant epilepsy and FCD, who carried a germline pathogenic variant in the DEPDC5 gene.
  • Investigated the presence and distribution of a potential second somatic DEPDC5 variant within the affected brain tissue.

Findings:

  • A second, somatic DEPDC5 pathogenic variant was identified, specifically localized to dysmorphic neurons within the FCD lesion.
  • The burden of this somatic mutation load demonstrated a direct correlation with both the density of dysmorphic neurons and the extent of the epileptogenic zone.

Implications:

  • These findings provide critical molecular and cellular insights into the pathogenesis of FCD and its role in driving drug-resistant epilepsy.
  • The study refines the conceptual understanding of the epileptogenic zone, highlighting the contribution of somatic mosaicism in specific neuronal populations.
  • Supports the hypothesized germline-plus-somatic "two-hit" model for FCD development, particularly involving DEPDC5 variants.

More Related Videos

Preparation of Dissociated Mouse Cortical Neuron Cultures18:02

Preparation of Dissociated Mouse Cortical Neuron Cultures

Published on: December 19, 2007

45.1K
Quantification of Filamentous Actin F-actin Puncta in Rat Cortical Neurons10:13

Quantification of Filamentous Actin F-actin Puncta in Rat Cortical Neurons

Published on: February 10, 2016

12.7K

Related Concept Videos

Mutations01:39

Mutations

Overview
94.4K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
43.8K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.8K
Nervous Tissue: Neuron Types01:19

Nervous Tissue: Neuron Types

Neurons, the fundamental units of the nervous system, can be classified based on both their structural and functional characteristics.
Structurally, neurons are categorized into three main types: multipolar, bipolar, and unipolar (or pseudounipolar). Multipolar neurons, which are the most common type in the brain and spinal cord, as well as all motor neurons, possess multiple dendrites and a single axon.
Bipolar neurons, on the other hand, have one primary dendrite and one axon. They are...
6.0K
Limiting Reactant02:27

Limiting Reactant

The relative amounts of reactants and products represented in a balanced chemical equation are often referred to as stoichiometric amounts. However, in reality, the reactants are not always present in the stoichiometric amounts indicated by the balanced equation.
69.4K
The Number e as a Limit01:29

The Number e as a Limit

The number e is a fundamental constant in calculus, playing a central role in describing continuous change, particularly exponential growth. It is most naturally defined through its relationship with the natural logarithm, which is the inverse of the exponential function with base e. This relationship allows e to be characterized using basic principles of differentiation rather than as an arbitrary numerical constant.A key property of the natural logarithm function, ln x, is that its derivative...
67