title: Functional studies of MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts.
abstract: Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on their protein/mRNA expression, or on their intracellular protein localization, or both.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Xie
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.forename: Ajit Singh
authors.initials: AS
authors.lastname: Dhaunchak
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Liping
authors.initials: L
authors.lastname: Kou
authors.forename: Mangmang
authors.initials: M
authors.lastname: Guo
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.forename: David
authors.initials: D
authors.lastname: Colman
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002681:China; D018389:Codon, Nonsense; D003560:Cysts / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D018389:Codon, Nonsense; C425069:MLC1 protein, human; D008565:Membrane Proteins; D050505:Mutant Proteins