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

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,...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature genetics 2011-02, Vol.43 (2), p.132-137
Hauptverfasser: Superti-Furga, Andrea, Lausch, Ekkehart, Janecke, Andreas, Bros, Matthias, Trojandt, Stefanie, Alanay, Yasemin, De Laet, Corinne, Hübner, Christian A, Meinecke, Peter, Nishimura, Gen, Matsuo, Mari, Hirano, Yoshiko, Tenoutasse, Sylvie, Kiss, Andrea, Machado Rosa, Rafael Fabiano, Unger, Sharon L, Renella, Raffaele, Bonafé, Luisa, Spranger, Jürgen, Unger, Sheila, Zabel, Bernhard
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:1061-4036
1546-1718
DOI:10.1038/ng.749