title: A common mutation and a novel mutation in Japanese patients with van der Knaap disease.
abstract: Van der Knaap disease, or megalencephalic leukoencephalopathy with subcortical cysts (MLC), is an autosomal recessive disorder clinically characterized by macrocephaly, ataxia, spasticity, and mental decline. Magnetic resonance imaging (MRI) shows swollen brain with diffuse white-matter abnormalities and subcortical cysts, particularly in the anterior-temporal region. Recently, the MLC1 gene was identified as the gene responsible for this disorder, and mutations in this gene were described in several patients. We studied three Japanese patients with van der Knaap disease at the molecular genetic level. Two of them were homozygous for a previously-described mutation, S93L, and one was a compound heterozygote for S93L and a novel mutation, 452-468del+g, which leads to frameshift with a premature termination codon. Combining our data with previous reports allowed us to estimate the molecular genetic basis of this disorder in seven Japanese patients. In summary, S93L was observed in six of seven (85.7%) patients at least in one allele, and ten of 14 (71.4%) alleles had this mutation. Therefore, S93L appears to be fairly frequent in Japanese patients with van der Knaap disease, and analysis for this mutation in DNA isolated from leukocytes would provide for an easy and precise diagnosis of this disorder in Japanese patients.
authors: Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. tsujino@ncnp.go.jp.
authors: Seiichi
authors: S
authors: Tsujino
authors: Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors: Naomi
authors: N
authors: Kanazawa
authors: Department of Pediatrics, Kitakyushu Rehabilitation Center for Children with Disabilities, Kitakyushu, Japan.
authors: Hitoshi
authors: H
authors: Yoneyama
authors: Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Masayuki
authors: M
authors: Shimono
authors: Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Akihiro
authors: A
authors: Kawakami
authors: Department of Neurology, Teikyo University School of Medicine, Tokyo, Japan.
authors: Yuuki
authors: Y
authors: Hatanaka
authors: Department of Neurology, Teikyo University School of Medicine, Tokyo, Japan.
authors: Teruo
authors: T
authors: Shimizu
authors: Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Oba
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology*; D003062:Codon; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D015140:Dementia, Vascular / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003062:Codon; D018076:DNA, Complementary; C425069:MLC1 protein, human; D008565:Membrane Proteins