title: Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts.
abstract: Mutations in the gene MLC1 are found in approximately 80% of the patients with the inherited childhood white matter disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC). Genetic linkage studies have not led to the identification of another disease gene. We questioned whether mutations in CLCN2, coding for the chloride channel protein 2 (ClC-2), are involved in MLC. Mice lacking this protein develop white matter abnormalities, which are characterized by vacuole formation in the myelin sheaths, strikingly similar to the intramyelinic vacuoles in MLC. Sequence analysis of CLCN2 at genomic DNA and cDNA levels in 18 MLC patients without MLC1 mutations revealed some nucleotide changes, but they were predicted to be nonpathogenic. Further, in electrophysiological experiments, one of the observed amino acid changes was shown to have no effect on the ClC-2-mediated currents. In conclusion, we found no evidence suggesting that the CLCN2 gene is involved in MLC.
authors.affiliation: Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands. gc.scheper@vumc.nl
authors.forename: Gert C
authors.initials: GC
authors.lastname: Scheper
authors.forename: Carola G M
authors.initials: CG
authors.lastname: van Berkel
authors.forename: Lilia
authors.initials: L
authors.lastname: Leisle
authors.forename: Koen E
authors.initials: KE
authors.lastname: de Groot
authors.forename: Ab
authors.initials: A
authors.lastname: Errami
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Jentsch
authors.forename: Marjo S
authors.initials: MS
authors.lastname: Van der Knaap
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D015140:Dementia, Vascular / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; C000715428:Clcn2 protein, mouse; D018076:DNA, Complementary; C425069:MLC1 protein, human; D008565:Membrane Proteins; D050505:Mutant Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins