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Functional Analyses of Mutations in HEPACAM Causing Megalencephalic Leukoencephalopathy
Author(s) -
Arnedo Tanit,
LópezHernández Tania,
Jeworutzki Elena,
CapdevilaNortes Xavier,
Sirisi Sònia,
Pusch Michael,
Estévez Raúl
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22622
Subject(s) - biology , leukoencephalopathy , genetics , mutation , computational biology , gene , medicine , disease
Megalencephalic leukoencephalopathy with subcortical cysts ( MLC ) is a rare type of leukodystrophy characterized by white matter edema. Autosomal‐recessive mutations in MLC 1 cause MLC type 1, and autosomal‐recessive or dominant mutations in HEPACAM (also called GLIALCAM ) cause MLC type 2 A and type 2 B , respectively. The role of MLC 1 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.