Functional Analyses of Mutations inHEPACAMCausing Megalencephalic Leukoencephalopathy
- 18 July 2014
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 35 (10), 1175-1178
- https://doi.org/10.1002/humu.22622
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.Keywords
Funding Information
- E-RARE 2 (CLC & MLC)
- ELA Foundation (2012-014C2B)
- icrea (ICREA Academia Prize 2009-2014)
- Saf (SAF 2012-31486)
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