A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study

• Published in: Brain & development (Tokyo. 1979) Vol. 25; no. 5; pp. 362 - 366
• Main Authors: Saijo, Harumi, Nakayama, Harumi, Ezoe, Takanori, Araki, Katsuhito, Sone, Sui, Hamaguchi, Hiroshi, Suzuki, Hisaharu, Shiroma, Naohide, Kanazawa, Naomi, Tsujino, Seiichi, Hirayama, Yoshito, Arima, Masataka
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2003; Elsevier Science
• Subjects: Adult; Biological and medical sciences; Brain Diseases - genetics; Central Nervous System Cysts - genetics; Central Nervous System Cysts - pathology; Cerebrovascular Disorders - genetics; Cerebrovascular Disorders - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia, Vascular - genetics; DNA Mutational Analysis; Heredodegenerative Disorders, Nervous System - genetics; Heredodegenerative Disorders, Nervous System - pathology; Humans; Leucine - genetics; Leukoencephalopathy; Magnetic Resonance Imaging; Male; Medical sciences; Megalencephalic leukoencephalopathy with subcortical cysts; Membrane Proteins - genetics; MLC1 gene; Molecular Biology - methods; Mutation; Neurology; Reverse Transcriptase Polymerase Chain Reaction - methods; Sequence Analysis, DNA; Serine - genetics; Tumors of the nervous system. Phacomatoses; MLC1 gene; Mutation; Leukoencephalopathy; Megalencephalic leukoencephalopathy with subcortical cysts; Cerebral cortex; Homozygosity; Codon; Missense mutation; Cyst; Ataxia; Benign neoplasm; Neurological disorder; Human; Nervous system diseases; Spasticity; Muscle tonus alteration; Nuclear magnetic resonance imaging; Japanese; Cerebral disorder; Genetic disease; Striated muscle disease; Deterioration; Central nervous system disease; Medical imagery; Subcortex; Macrocephaly
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/S0387-7604(03)00006-8

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor function with ataxia, spasticity and mental decline. It has been revealed that the mutations in the gene, KIAA0027, were responsible for MLC and the gene was renamed subsequently ‘ MLC1’. A 41-year-old Japanese male with MLC, in whom a homozygous missense mutation, T CG to T TG at codon 93 resulting in S93L, was detected in the MLC1 gene, was described. MRI revealed marked cerebral atrophy and enlargement of the ventricular system. The subject's motor function had severely deteriorated, while his cognitive function had maintained at the level of a 2-year-old for the past 10 years. The mutation in the MLC1 gene of the patient is considered to be a common mutation responsible for MLC in Japanese patients because the same mutation had been detected in two other Japanese patients with MLC.