Disrupted SOX10 Regulation of GJC2 Transcription Causes Pelizaeus-Merzbacher-Like Disease

被引：31

作者：

Osaka, Hitoshi ^{[1
,2
]}

Hamanoue, Haruka ^{[3
]}

Yamamoto, Ryoko ^{[4
]}

Nezu, Atsuo ^{[5
]}

Sasaki, Megumi ^{[4
]}

Saitsu, Hirotomo ^{[3
]}

Kurosawa, Kenji ^{[6
]}

Shimbo, Hiroko ^{[1
]}

Matsumoto, Naomichi ^{[3
]}

Inoue, Ken ^{[4
]}

机构：

[1] Kanagawa Childrens Med Ctr, Div Neurol, Clin Res Inst, Yokohama, Kanagawa 232855, Japan

[2] Kanagawa Canc Ctr Res Inst, Mol Pathol & Genet Div, Kanagawa, Japan

[3] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa, Japan

[4] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Retardat & Birth Defect Res, Kodaira, Tokyo 187, Japan

[5] Yokohama Ryoiku Iryo Ctr, Div Pediat Neurol, Yokohama, Kanagawa, Japan

[6] Kanagawa Childrens Med Ctr, Div Genet, Clin Res Inst, Yokohama, Kanagawa, Japan

来源：

ANNALS OF NEUROLOGY | 2010年 / 68卷 / 02期

关键词：

SPASTIC PARAPLEGIA; GJA12; MUTATIONS; CONNEXIN-32; MECHANISM;

D O I：

10.1002/ana.22022

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：250 / 254

页数：5

共 20 条

[1] Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10 [J].

Bondurand, N ;

Girard, M ;

Pingault, V ;

Lemort, N ;

Dubourg, O ;

Goossens, M .

HUMAN MOLECULAR GENETICS, 2001, 10 (24) :2783-2795

[2] GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy [J].

Bugiani, M. ;

Al Shahwan, S. ;

Lamantea, E. ;

Bizzi, A. ;

Bakhsh, E. ;

Moroni, I. ;

Balestrini, M. R. ;

Uziel, G. ;

Zeviani, M. .

NEUROLOGY, 2006, 67 (02) :273-279

[3] GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease [J].

Henneke, M. ;

Combes, P. ;

Diekmann, S. ;

Bertini, E. ;

Brockmann, K. ;

Burlina, A. P. ;

Kaiser, J. ;

Ohlenbusch, A. ;

Plecko, B. ;

Rodriguez, D. ;

Boespflug-Tanguy, O. ;

Gartner, J. .

NEUROLOGY, 2008, 70 (10) :748-754

[4] Connexin 32 promoter P2 mutations:: A mechanism of peripheral nerve dysfunction [J].

Houlden, H ;

Girard, M ;

Cockerell, C ;

Ingram, D ;

Wood, NW ;

Goossens, M ;

Walker, RWH ;

Reilly, MM .

ANNALS OF NEUROLOGY, 2004, 56 (05) :730-734

[5] Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations [J].

Inoue, K ;

Khajavi, M ;

Ohyama, T ;

Hirabayashi, S ;

Wilson, J ;

Reggin, JD ;

Mancias, P ;

Butler, IJ ;

Wilkinson, MF ;

Wegner, M ;

Lupski, JR .

NATURE GENETICS, 2004, 36 (04) :361-369

[6] PLP1-related inherited dysmyelinating disorders:: Pelizaeus-Merzbacher disease and spastic paraplegia type 2 [J].

Inoue, K .

NEUROGENETICS, 2005, 6 (01) :1-16

[7] Translation of SOX10 3′ untranslated region causes a complex severe neurocristopathy by generation of a deleterious functional domain [J].

Inoue, Ken ;

Ohyama, Tomoko ;

Sakuragi, Yosuke ;

Yamamoto, Ryoko ;

Inoue, Naoko A. ;

Yu Li-Hua ;

Goto, Yu-ichi ;

Wegner, Michael ;

Lupski, James R. .

HUMAN MOLECULAR GENETICS, 2007, 16 (24) :3037-3046

[8] Pelizaeus-Merzbacher-like disease: Female case report [J].

Nezu, A ;

Kimura, S ;

Uehara, S ;

Osaka, H ;

Kobayashi, T ;

Haraguchi, M ;

Inoue, K ;

Kawanishi, C .

BRAIN & DEVELOPMENT, 1996, 18 (02) :114-118

[9] Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins [J].

Orthmann-Murphy, Jennifer L. ;

Freidin, Mona ;

Fischer, Esther ;

Scherer, Steven S. ;

Abrams, Charles K. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (51) :13949-13957

[10] Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease [J].

Orthmann-Murphy, Jennifer L. ;

Enriquez, Alan D. ;

Abrams, Charles K. ;

Scherer, Steven S. .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2007, 34 (04) :629-641

← 1 2 →