Advertisement

neurogenetics

, Volume 12, Issue 3, pp 259–261 | Cite as

Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5

  • Takashi Matsukawa
  • Xuemin Wang
  • Rui Liu
  • Noel C. Wortham
  • Yuko Onuki
  • Akatsuki Kubota
  • Ayumi Hida
  • Hisatomo Kowa
  • Yoko Fukuda
  • Hiroyuki Ishiura
  • Jun Mitsui
  • Yuji Takahashi
  • Shigeki Aoki
  • Shunya Takizawa
  • Jun Shimizu
  • Jun Goto
  • Christopher G. Proud
  • Shoji TsujiEmail author
Letter to the Editors

Leukoencephalopathy with vanishing white matter (VWM) is a type of leukoencephalopathy with autosomal recessive inheritance. Magnetic resonance imaging (MRI) reveals diffuse leukoencephalopathy with lesions having cerebrospinal fluid (CSF)-like signals. The clinical presentations include progressive cerebellar ataxia, spasticity, and mental decline. The course is chronic progressive with episodes of rapid deterioration following a minor head trauma. Mutations in the five gene-encoding subunits of the translation initiation factor eIF2B, EIF2B1-5, have been identified as the causative mutations for VWM. Although the age at onset of VWM is usually 2–6 years, patients with adult onset have been described. All adult-onset cases except one have been found to be associated with mutations in EIF2B5 [1]. We report cases of adult-onset VWM with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5, which showed decreased eIF2B activities.

Case 1:

A Japanese woman aged 56 who experienced...

Keywords

Cerebellar Ataxia Homozygous Mutation Minor Head Trauma Homozygous Region Progressive Cerebellar Ataxia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported in part by KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas, Innovative Areas, Global COE Program for Chemical Biology of the Diseases, and Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant-in-Aid for Research on Intractable Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Welfare and Labour, Japan. CGP gratefully acknowledges the support from the UK Biotechnology and Biotechnology Research Council.

Disclosure

The experiments comply with the current laws of the country in which they were performed. The authors report no conflicts of interest.

Supplementary material

10048_2011_284_MOESM1_ESM.ppt (1.3 mb)
Supplementary Fig. 1 Brain MRI of cases 1, 2, and 3. T1-weighted MRI showed diffuse hypointense lesions in the cerebral white matter (A, D, and G), while T2-weighted MRI showed diffuse hyperintense lesions in the cerebral white matter (B, E, and H). FLAIR imaging revealed that some of the white matter lesions adjacent to the lateral ventricles showed signal intensities identical to those of CSF (C, F, and I). (PPT 1,307 kb)
10048_2011_284_MOESM2_ESM.ppt (618 kb)
Supplementary Fig. 2 Multilinkage analyses of cases 1, 2 and 3. Case 1: Multipoint parametric linkage study (autosomal recessive model) using the 100K SNP array (A) revealed homozygous regions including the locus for EIF2B1 or EIF2B2 (red arrows) and direct nucleotide sequence analysis of EIF2B confirmed the novel mutation (p.Val85Glu) in EIF2B2 (Fig. 1a). Case 2: A homozygous novel mutation (p.Asp270His) in EIF2B5 was identified (Fig. 1b) in the homozygous region on chromosome 3 (red arrow) (B). Case 3: A homozygous novel mutation (p.Leu27Gln) in EIF2B3 was identified (Fig. 1c) in the homozygous region on chromosome 1 (red arrow) (C) (PPT 618 kb)

References

  1. 1.
    Labauge P, Horzinski L, Ayrignac X, Blanc P, Vukusic S, Rodriguez D, Mauguiere F, Peter L, Goizet C, Bouhour F, Denier C, Confavreux C, Obadia M, Blanc F, de Sèze J, Fogli A, Boespflug-Tanguy O (2009) Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases. Brain 132:2161–2169PubMedCrossRefGoogle Scholar
  2. 2.
    Li W, Wang X, van der Knaap MS, Proud CG (2004) Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. Mol Cell Biol 24:3295–3306PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Takashi Matsukawa
    • 1
  • Xuemin Wang
    • 2
  • Rui Liu
    • 2
  • Noel C. Wortham
    • 2
  • Yuko Onuki
    • 3
  • Akatsuki Kubota
    • 1
  • Ayumi Hida
    • 1
  • Hisatomo Kowa
    • 4
  • Yoko Fukuda
    • 1
  • Hiroyuki Ishiura
    • 1
  • Jun Mitsui
    • 1
  • Yuji Takahashi
    • 1
  • Shigeki Aoki
    • 5
  • Shunya Takizawa
    • 3
  • Jun Shimizu
    • 1
  • Jun Goto
    • 1
  • Christopher G. Proud
    • 2
  • Shoji Tsuji
    • 1
    Email author
  1. 1.Department of Neurology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.School of Biological Sciences, Life Sciences BuildingUniversity of SouthamptonSouthamptonUK
  3. 3.Department of Neurology, Graduate School of MedicineUniversity of TokaiKanagawaJapan
  4. 4.Department of Neurology, Graduate School of MedicineKobe UniversityHyogoJapan
  5. 5.Department of Radiology, Graduate School of MedicineUniversity of JuntendoTokyoJapan

Personalised recommendations