J Clin Neurol.  2017 Oct;13(4):426-428. 10.3988/jcn.2017.13.4.426.

A Novel GFAP Mutation in Late-Onset Alexander Disease Showing Diffusion Restriction

• Nam TS
• Oh J
• Levy M
• Kang KW
• Choi SY
• Kim MK

• KMID: 2392141
• DOI: http://doi.org/10.3988/jcn.2017.13.4.426

Abstract

No abstract available.

MeSH Terms

Alexander Disease*
Diffusion*

Figure

• 

  Fig. 1 MRI findings and mutational analysis of the patient. A: T2-weighted axial MRI image showing high-signal-intensity lesions in the bilateral periventricular WM with frontal predominance. B: T1-weighted sagittal MRI image showing atrophy in the brainstem, cerebellum, and upper cervical cord as well as thinning of the corpus callosum. C, D, and E: Axial fluid-attenuated inversion recovery MRI images showing abnormal hyperintensities along the pia in the midbrain (C), pons (D), medulla oblongata, and around the fourth ventricle (E). F and G: Axial DWI images showing multifocal hyperintensities within the periventricular WM and cerebral cortex. H and I: DWI images obtained 1 year later showing newly developed multifocal small hyperintensities in the right cortical region as well as the previously existing lesions. J: Electropherogram of the patient reveals a nonsynonymous heterozygous A-to-G missense mutation (c.1087A>G, p.Ile363Val, red arrow) in exon 6 of the GFAP. K: Representative electropherogram of GFAP from a normal control. L: The p.Ile363 residue is highly conserved, and found in evolutionary distant orthologs down to zebra fish. The sequences were derived from GenBank with the following accession numbers of the orthologs: Homo sapiens (NM_002055.4), Bos taurus (cattle; NM_174065.2), Mus musculus (house mouse; NM_010277.3), Tursiops truncatus (dolphin; XM_019939330.1), Gallus gallus (chicken; XM_418091.5), Crocodylus porosus (Australian saltwater crocodile; XM_019554575.1), Chelonia mydas (green sea turtle; XM_007053824.1), and Danio rerio (zebra fish; NM_131373.2). DWI: diffusion-weighted MRI, GFAP: glial fibrillary acidic protein gene, MRI: magnetic resonance imaging, WM: white matter.

Reference

1. Prust M, Wang J, Morizono H, Messing A, Brenner M, Gordon E, et al. GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology. 2011; 77:1287–1294. PMID: 21917775.

2. Graff-Radford J, Schwartz K, Gavrilova RH, Lachance DH, Kumar N. Neuroimaging and clinical features in type II (late-onset) Alexander disease. Neurology. 2014; 82:49–56. PMID: 24306001.

3. van der Voorn JP, Pouwels PJ, Salomons GS, Barkhof F, van der. Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter. Neuroradiology. 2009; 51:669–675. PMID: 19484233.

4. Karaarslan E, Arslan A. Diffusion weighted MR imaging in non-infarct lesions of the brain. Eur J Radiol. 2008; 65:402–416. PMID: 17555903.