Nasu–Hakola disease with a splicing mutation of TREM2 in a Japanese family
Article first published online: 22 DEC 2010
© 2010 The Author(s). European Journal of Neurology © 2010 EFNS
European Journal of Neurology
Volume 18, Issue 9, pages 1179–1183, September 2011
How to Cite
Numasawa, Y., Yamaura, C., Ishihara, S., Shintani, S., Yamazaki, M., Tabunoki, H. and Satoh, J.-I. (2011), Nasu–Hakola disease with a splicing mutation of TREM2 in a Japanese family. European Journal of Neurology, 18: 1179–1183. doi: 10.1111/j.1468-1331.2010.03311.x
- Issue published online: 11 AUG 2011
- Article first published online: 22 DEC 2010
- Received 28 September 2010 Accepted 18 November 2010
Figure S1. The c.482+2T>C mutation induces exon 3 skipping. The ORF of TREM2 amplified by PCR was cloned in the vector. Four distinct clones were processed for sequencing analysis. The panels (a–d) represent (a) variant 1 with deletion of exon 3, composed of 157 amino acids, (b) variant 2 with deletion of exons 3 and 4, composed of 135 amino acids, (c) variant 3 with deletion of exons 2 and 3, composed of 40 amino acids, and (d) variant 4 with deletion of exons 2, 3, and 4, composed of 18 amino acids. The stop codon is underlined in variants 2 and 4.
Figure S2. Validation of microarray data by qRT-PCR. The microarray data was validated by quantitative RT-PCR on LightCycler ST300 (Roche Diagnostics). The panels represent (a) RGS1, (b) CD163, (c) GABRG2, and (d) SYT1. The expression levels of each gene were standardized against those of G3PDH. Frontal lobe cDNA of NC (the normal control), NHD (the patient 1), ALS1 and ALS2 (two patients with amyotrophic lateral sclerosis), and AD1 and AD2 (two patients with Alzheimer disease), were analyzed.
Figure S3. Molecular network of 136 upregulated and 188 downregulated genes in the brain of a NHD patient with TREM2 mutation. By Ingenuity Pathways Analysis (IPA) of brain transcriptome data of the patient 1, 136 upregulated genes constitute the network of 64 focused genes (red) that has the most significant relationship with inflammatory response, cellular movement, and immune cell trafficking (P = 1.00E-116) (panel a), while 188 downregulated genes constitute the network of 91 focused genes (green) that has the most significant relationship with cell-to-cell signaling and interaction, nervous system development and function, and genetic disorder (P = 1.00E-168) (panel b).
Table S1. The list of 136 upregulated genes in the brain of a NHD patient with TREM2 mutation.
Table S2. The list of 188 downregulated genes in the brain of a NHD patient with TREM2 mutation.
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