title: Functional analyses of mutations in HEPACAM causing megalencephalic leukoencephalopathy.
abstract: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy characterized by white matter edema. Autosomal-recessive mutations in MLC1 cause MLC type 1, and autosomal-recessive or dominant mutations in HEPACAM (also called GLIALCAM) cause MLC type 2A and type 2B, respectively. The role of MLC1 and HEPACAM is unknown, although they have been related with the processes of cell-volume regulation and potassium siphoning by astrocytes. Previous studies with some of the mutations identified in HEPACAM showed that most of them are associated with a trafficking defect. Here, we analyzed biochemically and functionally most mutations identified up-to-date in HEPACAM. Our results allow classifying the effect of mutations in different subtypes and we indicate different cellular mechanisms that lead to MLC pathogenesis.
authors.affiliation: Sección de Fisiología, Departamento de Ciencias Fisiológicas II, University of Barcelona, Barcelona, Spain; U-750, Centro de Investigación en red de enfermedades raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Tanit
authors.initials: T
authors.lastname: Arnedo
authors.forename: Tania
authors.initials: T
authors.lastname: López-Hernández
authors.forename: Elena
authors.initials: E
authors.lastname: Jeworutzki
authors.forename: Xavier
authors.initials: X
authors.lastname: Capdevila-Nortes
authors.forename: Sònia
authors.initials: S
authors.lastname: Sirisi
authors.forename: Michael
authors.initials: M
authors.lastname: Pusch
authors.forename: Raúl
authors.initials: R
authors.lastname: Estévez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics; D003560:Cysts / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D018118:Chloride Channels; C487620:HEPACAM protein, human; D011506:Proteins
keywords: GLIALCAM; HEPACAM; astrocyte; chloride channels; leukodystrophy