Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity

被引：130

作者：

Lausch, Ekkehart ^{[1
]}

Janecke, Andreas ^{[2
,3
]}

Bros, Matthias ^{[4
]}

Trojandt, Stefanie ^{[4
]}

Alanay, Yasemin ^{[5
]}

De Laet, Corinne ^{[6
]}

Huebner, Christian A. ^{[7
]}

Meinecke, Peter ^{[8
]}

Nishimura, Gen ^{[9
]}

Matsuo, Mari ^{[10
]}

Hirano, Yoshiko ^{[10
]}

Tenoutasse, Sylvie ^{[6
]}

Kiss, Andrea ^{[11
,12
]}

Machado Rosa, Rafael Fabiano ^{[11
,12
]}

Unger, Sharon L. ^{[13
]}

Renella, Raffaele ^{[14
,15
,16
]}

Bonafe, Luisa ^{[16
]}

Spranger, Juergen ^{[1
]}

Unger, Sheila ^{[1
,17
]}

Zabel, Bernhard ^{[1
]}

Superti-Furga, Andrea ^{[1
,16
]}

机构：

[1] Univ Freiburg, Freiburg Univ Hosp, Ctr Pediat & Adolescent Med, Freiburg, Germany

[2] Innsbruck Med Univ, Dept Pediat 2, Innsbruck, Austria

[3] Innsbruck Med Univ, Div Human Genet, Innsbruck, Austria

[4] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Dermatol, Mainz, Germany

[5] Hacettepe Univ, Fac Med, Dept Pediat, Pediat Genet Unit, TR-06100 Ankara, Turkey

[6] Queen Fabiola Childrens Univ Hosp, Nutr & Metab Unit, Brussels, Belgium

[7] Univ Jena, Univ Hosp Jena, Inst Human Genet, Jena, Germany

[8] Childrens Hosp Altona, Clin Genet Unit, Hamburg, Germany

[9] Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Imaging, Tokyo, Japan

[10] Tokyo Womens Med Univ, Dept Pediat, Tokyo, Japan

[11] Univ Fed Ciencias Saude Porto Alegre, Div Clin Genet, Porto Alegre, RS, Brazil

[12] Univ Fed Ciencias Saude Porto Alegre, Grad Program Pathol, Porto Alegre, RS, Brazil

[13] Univ Toronto, Mt Sinai Hosp, Div Neonatol, Toronto, ON M5G 1X5, Canada

[14] Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA

[15] Dana Farber Canc Inst, Boston, MA 02115 USA

[16] CHU Vaudois, Dept Pediat, CH-1011 Lausanne, Switzerland

[17] CHU Vaudois, Dept Med Genet, CH-1011 Lausanne, Switzerland

来源：

NATURE GENETICS | 2011年 / 43卷 / 02期

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; DENDRITIC CELLS; MULTIPLE-SCLEROSIS; T-CELLS; OSTEOPONTIN EXPRESSION; STAPHYLOCOCCUS-AUREUS; ACP; SPONDYLOENCHONDRODYSPLASIA; SURVIVAL; DISEASE;

D O I：

10.1038/ng.749

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an altered cytokine profile and are more potent than matched control cells in stimulating allogeneic T cell proliferation in mixed lymphocyte reactions. These findings shed new light on the role of osteopontin and its regulation by TRAP in the pathogenesis of common autoimmune disorders.

引用

页码：132 / U79

页数：8

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