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Brain Dev. 2015 Nov;37(10):960-6. doi: 10.1016/j.braindev.2015.03.003. Epub 2015 Apr 3.

Mutations in the genes encoding eukaryotic translation initiation factor 2B in Japanese patients with vanishing white matter disease.

Author information

1
Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
2
Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
3
Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
4
Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.
5
Department of Pediatrics, Tsukuba University, Tsukuba, Japan.
6
Department of Neurology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
7
Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, Sanda, Japan.
8
Department of Pediatrics, Okinawa Chubu Hospital, Uruma, Japan.
9
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
10
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
11
Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.

Abstract

OBJECTIVE:

Vanishing white matter disease (VWM) is a chronic, progressive leukoencephalopathy associated with episodes of rapid deterioration following minor stress events such as head traumas or infectious disorders. The white matter of the patients with VWM exhibits characteristic radiological findings.

METHOD:

The genes encoding all five subunits of eukaryotic translation initiation factor 2B (EIF2B) were analyzed in patients, who were tentatively diagnosed with VWM, by Sanger sequencing.

RESULTS:

Seven mutations were identified in the genes encoding the subunits 1, 2, 4, and 5 of EIF2B. Among them, one mutation (p.V83E) in the subunit 2 (EIF2B2) was recurrently identified in three alleles, indicating the most common mutation in Japanese patients with VWM. Two patients were homozygous, and the other four patients were compound heterozygous.

CONCLUSION:

All patients showed white matter abnormalities with various degrees. One patient showed manifestations of end-stage VWM disease. Some patients showed late onset and slow progression associated with brain magnetic resonance imaging displaying T2 high intensity only in the deep white matter. There was clinical heterogeneity among patients with VWM.

KEYWORDS:

Eukaryotic translation initiation factor 2B (EIF2B); Leukoencephalopathy; Mutation; Vanishing white matter disease (VWM)

PMID:
25843247
DOI:
10.1016/j.braindev.2015.03.003
[Indexed for MEDLINE]

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