Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Letter to the Editor Eur Neurol 2007;57:57–58 DOI: 10.1159/000097120 Novel Mutation in EIF2B Gene in a Case of Adult-Onset Leukoencephalopathy with Vanishing White Matter Masaru Matsui a Kotaro Mizutani d Hiroaki Ohtake e Yukio Miki b Koichi Ishizu b Hidenao Fukuyama c Takayoshi Shimohata e Osamu Onodera f Masatoyo Nishizawa e Yoshihiro Takayama g Hiroshi Shibasaki a, c Departments of a Neurology and b Nuclear Medicine and Diagnostic Imaging and c Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, d Department of Neurology, Sakakibara Hakuho Hospital, Mie, Departments of e Neurology and f Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, and g Department of Speech Physiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan close to that of the cerebrospinal fluid in some parts. All of these results were con- sistent with a clinical diagnosis of VWM [1, 4]. In addition, the disease progression was very slow, and her clinical state re- mained nearly stable for several years. A genetic analysis was performed, us- ing a method previously described [6]. In brief, DNA was extracted from a blood sample after obtaining informed consent from the patient. The entire coding re- gions of EIF2B2 and EIF2B5, which en- code eIF2B and eIF2B , respectively, Dear Sir, Leukoencephalopathy with vanishing white matter (VWM) [1], also referred to as childhood ataxia with diffuse central ner- vous system hypomyelination (CACH) [2], is a newly described white matter disease characterized by autosomal recessive in- heritance, chronic progressive cerebellar ataxia, spasticity and unique MRI find- ings. Recently, mutations in the 5 genes (EIF2B1 to EIF2B5) encoding the subunits of the eukaryotic translation initiation fac- tor 2B (eIF2B), which plays an important role in the regulation of translation initia- tion of protein synthesis, have been identi- fied as the cause of VWM [3, 4]. We previ- ously reported the first case of adult-onset VWM of Asian origin based on clinical di- agnostic criteria [5]. Herein, we report the findings of a genetic study of this case that identified a novel EIF2B mutation. Our female patient developed slowly progressive gait disturbance and hand clumsiness at the age of 42 [5]. Neurologi- cal findings included cerebellar ataxia, ex- aggerated deep tendon reflexes with bilat- eral Babinski sign and mild mental de- cline. Cranial MRI showed that the cere- bral white matter was symmetrically and diffusely abnormal with a signal intensity Received: August 25, 2006 Accepted: September 7, 2006 Published online: November 20, 2006 Dr. Masaru Matsui Department of Neurology, Kanazawa Medical University 1-1 Daigaku, Uchinada, Kahoku-gun Ishikawa 920-0293 (Japan) Tel. +81 76 286 2211, Fax +81 76 286 3259, E-Mail masarum@kanazawa-med.ac.jp © 2007 S. Karger AG, Basel 0014–3022/07/0571–0057$23.50/0 Accessible online at: www.karger.com/ene were amplified using the PCR primer sets listed at http://www.vumc.nl/whitematter. After purification of the PCR products, di- rect sequencing was performed using an ABI PRISM 3100 Genetic Analyzer (Ap- plied Biosystems, Foster City, Calif., USA). The result revealed a novel G1459A mis- sense mutation in the EIF2B5 gene (fig. 1A). This mutation in EIF2B5 leads to a substi- tution of glutamic acid for lysine in eIF2B at position 487 (E487K). Forty-four unre- lated Japanese control subjects did not show this mutation (fig. 1B). Fig. 1. Sequencing electropherogram images showing the G1459A transition in EIF2B5 in the patient (A, arrow) compared with a control subject (B, arrow).