ArticleAmerican journal of human genetics2011
Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism.
Article in American journal of human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94 citing papers in PubMed, 193 citations in OpenAlex.
- Patient and Family Perspectives on Clinical Outcomes in Therapy Trials in Megalencephalic Leukoencephalopathy with Subcortical Cysts: An Open Inventory.Neuropediatrics · 2026Article
- MLC1 alteration in human iPSCs give rise to disease-like cellular vacuolation phenotype in the astrocyte lineage.Orphanet journal of rare diseases · 2026Article
- Multiple molecular mimics in Epstein Barr Nuclear Antigen-1, and the pathogenesis of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Altered Mechanical Properties of Astrocytes Lacking MLC1: Implications for the Leukodystrophy MLC.Glia · 2026Article
- Megalencephalic leukoencephalopathy with subcortical cysts: a multicenter Italian experience.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Observational
- Swelling-induced calcium signaling in wild-type andFrontiers in cellular neuroscience · 2026Article
- Genomic landscape of autism spectrum disorder in Brazil.Genetics and molecular biology · 2026Article
- Megalencephalic Leukoencephalopathy Type 2B.Indian journal of pediatrics · 2026Article
- Glial Ion Channels in Myelin Pathophysiology: Insights from Leukodystrophies.Life (Basel, Switzerland) · 2025Review
- Article
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- 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
- Understanding rare variant contributions to autism: lessons from dystrophin-deficient model.NPJ genomic medicine · 2025Article
- Psychotic attack during the clinical course of megalencephalic leukoencephalopathy with subcortical cysts: a case report.European child & adolescent psychiatry · 2025Article
- Modulator of VRAC Current 1 Is a Potential Target Antigen in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Intragenic homozygous duplication in HEPACAM is associated with megalencephalic leukoencephalopathy with subcortical cysts type 2A.Neurogenetics · 2024Article
- Expanding the phenotypic spectrum ofBrain communications · 2024Article
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- Glial Cell Adhesion Molecule (GlialCAM) Determines Proliferative versus Invasive Cell States in Glioblastoma.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation.Nature communications · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed that some patients without MLC1 mutations display the classical phenotype; others improve or become normal but retain macrocephaly. To find another MLC-related gene, we used quantitative proteomic analysis of affinity-purified MLC1 as an alternative approach and found that GlialCAM, an IgG-like cell adhesion molecule that is also called HepaCAM and is encoded by HEPACAM, is a direct MLC1-binding partner. Analysis of 40 MLC patients without MLC1 mutations revealed multiple different HEPACAM mutations. Ten patients with the classical, deteriorating phenotype had two mutations, and 18 patients with the improving phenotype had one mutation. Most parents with a single mutation had macrocephaly, indicating dominant inheritance. In some families with dominant HEPACAM mutations, the clinical picture and magnetic resonance imaging normalized, indicating that HEPACAM mutations can cause benign familial macrocephaly. In other families with dominant HEPACAM mutations, patients had macrocephaly and mental retardation with or without autism. Further experiments demonstrated that GlialCAM and MLC1 both localize in axons and colocalize in junctions between astrocytes. GlialCAM is additionally located in myelin. Mutant GlialCAM disrupts the localization of MLC1-GlialCAM complexes in astrocytic junctions in a manner reflecting the mode of inheritance. In conclusion, GlialCAM is required for proper localization of MLC1. HEPACAM is the second gene found to be mutated in MLC. Dominant HEPACAM mutations can cause either macrocephaly and mental retardation with or without autism or benign familial macrocephaly.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.