TY - JOUR
T1 - Analysis of CLCN2 as Candidate Gene for Megalencephalic Leukoencephalopathy with Subcortical Cysts
AU - Scheper, G.C.
AU - van Berkel, C.G.M.
AU - Leisle, L.
AU - de Groot, K.E.
AU - Errami, A.
AU - Jentsch, T.J.
AU - van der Knaap, M.S.
PY - 2010
Y1 - 2010
N2 - 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. © 2010, Mary Ann Liebert, Inc.
AB - 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. © 2010, Mary Ann Liebert, Inc.
U2 - 10.1089/gtmb.2009.0148
DO - 10.1089/gtmb.2009.0148
M3 - Article
SN - 1945-0265
VL - 14
SP - 255
EP - 257
JO - Genetic Testing and Molecular Biomarkers
JF - Genetic Testing and Molecular Biomarkers
IS - 2
ER -
