1. Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease.
- Author
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Osaka, Hitoshi, Hamanoue, Haruka, Yamamoto, Ryoko, Nezu, Atsuo, Sasaki, Megumi, Saitsu, Hirotomo, Kurosawa, Kenji, Shimbo, Hiroko, Matsumoto, Naomichi, and Inoue, Ken
- Abstract
Mutations in the gap junction protein gamma-2 gene, GJC2, cause a central hypomyelinating disorder; Pelizaeus-Merzbacher-like disease (PMLD; MIM311601). Using a homozygosity mapping and positional candidate gene approach, we identified a homozygous mutation (c.-167A>G) within the GJC2 promoter at a potent SOX10 binding site in a patient with mild PMLD. Functionally, this mutation completely abolished the SOX10 binding and attenuated GJC2 promoter activity. These findings suggest not only that the SOX10-to- GJC2 transcriptional dysregulation is a cause of PMLD, but also that GJC2 may be in part responsible for the central hypomyelination caused by SOX10 mutations. ANN NEUROL 2010;68:250-254 [ABSTRACT FROM AUTHOR]
- Published
- 2010
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