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Functional Studies of MLC1 Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts

By Han Xie, Jingmin Wang, Ajit Singh Dhaunchak, Jing Shang, Liping Kou, Mangmang Guo, Ye Wu, Qiang Gu, David Colman, Xiru Wu and Yuwu Jiang

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 MLC1wt 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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3293920
Provided by: PubMed Central
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