Skip to main content
Article thumbnail
Location of Repository

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


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:
Provided by: PubMed Central

Suggested articles


  1. (2003). A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study.
  2. (2003). A common mutation and a novel mutation in Japanese patients with van der Knaap disease.
  3. (2001). A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree.
  4. (2008). Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin–glycoprotein complex.
  5. (2003). Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC).
  6. (2007). Expression patterns of MLC1 protein in the central and peripheral nervous systems.
  7. (2003). Genetic heterogeneity of megalencephalic leukoencephalopathy and subcortical cysts.
  8. (2002). Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts.
  9. (2004). Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation.
  10. (1995). Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children.
  11. (2004). Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts.
  12. (2011). Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation.
  13. (2002). Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in Israeli patients and a higher than expected carrier rate among Libyan Jews.
  14. (2006). Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1.
  15. (2005). Megarbane A
  16. (2005). MLC1: a novel protein in distal astroglial processes.
  17. (2007). MLC1is associated with the dystrophin–glycoprotein complex at astrocytic endfeet.
  18. (2006). MR imaging and 1H-MR spectroscopy of a case of van der Knaap disease.
  19. (2001). Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts.
  20. (2003). Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and schizophrenia allelic disorders?
  21. (1999). Voltage-gated ion channels and hereditary disease.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.