title: MLC1 mutations in Japanese patients with megalencephalic leukoencephalopathy with subcortical cysts.
abstract: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive neurological disorder manifesting early onset macrocephaly and delayed-onset neurological deterioration. Characteristic radiological findings revealed by brain magnetic resonance imaging are the most important factors for obtaining a clinical diagnosis. In this study, we analyzed the causative gene, MLC1, in seven unrelated Japanese patients. The most common mutation in our study was p.S93L; this mutation was observed in 11 alleles (78.6%). The second most common mutation, p.A275D, was observed in two alleles (14.3%). A novel single-nucleotide deletion, c.578delG (p.V194Sfs*2), was identified in one allele. As the clinical severities of patients with MLC were variable even among those sharing identical genotypes, this condition may be modified by environmental factors, modifier genes or epigenetic factors.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences , Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Neurology, Kumamoto Saisyunsou National Hospital , Koshi, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Neurology, Wakayama Medical University , Wakayama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, Musashino Red Cross Hospital , Musashino, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kohji
authors.affiliation: Department of Pediatrics, Sumitomo Hospital , Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Kumamoto-Ashikita Medical Center for Severe Motor and Intellectual Disabilities , Kumamoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsubasa
authors.affiliation: Department of Pediatrics, University of Tokyo , Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences , Tokyo, Japan.
authors.forename: Toshiyuki
authors.identifier: 0000-0002-9484-3505
authors.initials: T
authors.lastname: Yamamoto