Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome

被引:63
作者
Albert, Michael H. [1 ]
Notarangelo, Luigi D. [2 ,3 ]
Ochs, Hans D. [4 ,5 ]
机构
[1] Univ Munich, Dept Pediat Hematol Oncol, Dr von Haunersches Kinderspital, Munich, Germany
[2] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Boston, MA USA
[3] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA
[4] Univ Washington, Dept Pediat, Seattle, WA 98195 USA
[5] Ctr Immun & Immunotherapy, Seattle Childrens Res Inst, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
gene therapy; hematopoietic stem cell transplantation; WAS gene; Wiskott-Aldrich syndrome; X-linked neutropenia; X-linked thrombocytopenia; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SYNDROME PROTEIN-DEFICIENCY; X-LINKED THROMBOCYTOPENIA; ACTIN POLYMERIZATION; GENE-THERAPY; T-CELLS; B-CELLS; WASP; MUTATIONS;
D O I
10.1097/MOH.0b013e32834114bc
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review The Wiskott-Aldrich syndrome (WAS), caused by mutations in the WAS gene, is a complex and diverse disorder with X-linked inheritance. This review focuses on recent developments in the understanding of its basic pathophysiology, diverse clinical phenotypes and optimal patient management including novel therapies. Recent findings The protein encoded by the WAS gene is a multifunctional signaling element expressed in immune and hematopoietic cells that plays a critical role in cytoskeletal reorganization, immune synapse formation and intracellular signaling. The type of specific mutation, its location within the gene and its effect on protein expression play a major role in determining an individual patient's clinical phenotype. Recent clinical observations and molecular studies have created a sophisticated picture of the disease spectrum. The improved outcome of stem cell transplantation from related and unrelated matched donors and promising early results from the first clinical gene therapy trial have added new therapeutic options for these patients. Summary Classic WAS, X-linked thrombocytopenia and X-linked neutropenia are caused by WAS gene mutations, each having a distinct pattern of clinical symptoms and disease severity. New developments in the understanding of these syndromes and novel therapeutic options will have a major impact on the treatment of individuals with WAS mutations.
引用
收藏
页码:42 / 48
页数:7
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