ArticleHuman molecular genetics2020
Structural basis for the dominant or recessive character of GLIALCAM mutations found in leukodystrophies.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Intragenic homozygous duplication in HEPACAM is associated with megalencephalic leukoencephalopathy with subcortical cysts type 2A.Neurogenetics · 2024Article
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts.International journal of molecular sciences · 2022Review
- Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022Review
- Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations.Scientific reports · 2021Article
- Article
- Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) promotes glioblastoma cell invasion in the brain microenvironment.Oncogene · 2020Article
- Article
- Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy.Frontiers in cellular neuroscience · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a type of leukodystrophy characterized by white matter edema, and it is caused mainly by recessive mutations in MLC1 and GLIALCAM genes. These variants are called MLC1 and MLC2A with both types of patients sharing the same clinical phenotype. In addition, dominant mutations in GLIALCAM have also been identified in a subtype of MLC patients with a remitting phenotype. This variant has been named MLC2B. GLIALCAM encodes for an adhesion protein containing two immunoglobulin (Ig) domains and it is needed for MLC1 targeting to astrocyte-astrocyte junctions. Most mutations identified in GLIALCAM abolish GlialCAM targeting to junctions. However, it is unclear why some mutations behave as recessive or dominant. Here, we used a combination of biochemistry methods with a new developed anti-GlialCAM nanobody, double-mutants and cysteine cross-links experiments, together with computer docking, to create a structural model of GlialCAM homo-interactions. Using this model, we suggest that dominant mutations affect different GlialCAM-GlialCAM interacting surfaces in the first Ig domain, which can occur between GlialCAM molecules present in the same cell (cis) or present in neighbouring cells (trans). Our results provide a framework that can be used to understand the molecular basis of pathogenesis of all identified GLIALCAM mutations.
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