Category: Timeline Stories

Timeline Stories

What causes seizures in MLC?

Using two of the previously generated mouse models, this is the first in depth study on the occurrence and cause of seizures in MLC. Specifically, dysregulation of ions and water were found to cause seizures in this disease.   Read paper

Timeline Stories

MLC disease in Chinese patients

This study examines the clinical and genetic findings in a group of Chinese MLC patients and tracks the disease progression over time. This is important to expand the disease spectrum and prevalence of MLC. Read paper

Timeline Stories

The first animal models of MLC

These studies include the generation and characterization of the first animal  models (mouse, zebrafish) for MLC. They describe mice or zebrafish with mutations in either MLC1 or GlialCAM. As a result, these animals show key features of MLC and can be used to study aspects of the disease. 2014: Paper 1, Paper 2, Paper 3..Read More

Timeline Stories

Defects in ion and water movement cause MLC

These four studies are the first to demonstrate a potential function of the MLC1 protein in regulating ion channels and transporters important for controlling ions and water homeostasis, which affects the volume of cells. These findings suggest that MLC may be caused by the fact that astrocytes in the brain are chronically swollen because of..Read More

Timeline Stories

How mutations in MLC1 and GlialCAM cause MLC

This study provides further proof that MLC1 and GlialCAM interact with each other. Mutations in MLC1 were found to decrease the amount of MLC1 protein in the brain while mutations in GlialCAM caused improper localization of these proteins. Read paper

Timeline Stories

Identification of the second MLC gene: GLIALCAM

In this paper, researchers identify the second MLC gene: HEPACAM (renamed to GLIALCAM). Patients with two so-called recessive GLIALCAM mutations had the classical form of MLC while patients with one specific dominant mutation had the improving phenotype. The authors also demonstrated that GlialCAM interacts with MLC1 and is expressed in neurons and astrocytes. Read paper

Timeline Stories

Discovery of the classic and improving phenotypes

This study is the first to describe that MLC patients without MLC1 mutations can show two different clinical phenotypes: they either have classical MLC or they show an improving phenotype.    Read paper

Timeline Stories

MLC is a conformational disease

This study shows that most mutations in MLC1 cause problems with proper folding of the protein into the correct structure and therefore, pharmacological strategies that improve MLC1 expression could be useful to treat MLC patients. Read paper

Timeline Stories

MLC is a disease affecting astrocytes

This study shows that the MLC1 protein is present mainly in a certain type of supportive brain cells called astrocytes, suggesting that these cells may be the most affected in MLC. Read paper  

Timeline Stories

Discovery of the first MLC gene

Prior to this research paper, there was no causal gene identified to cause MLC. Here, researchers discovered the first MLC gene, named MLC1, encoding a membrane protein. This discovery allows for patients to be diagnosed through genetic testing and paves the way for future studies on the function of the MLC1 protein. Read paper