Intronic SH2D1A mutation with impaired SAP expression and agammaglobulinemia

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• 作者：Mike Recher^a ; ^b ; ^c ; ¹ ; ^{rechermike@uhbs.ch} ; Ari J. Fried^a ; ¹ ; Michel J. Massaad^a ; Hye Young Kim^a ; Michela Rizzini^d ; Francesco Frugoni^a ; Jolan E. Walter^a ; ^f ; Divij Mathew^a ; Hermann Eibel^e ; Christoph Hess^b ; ^c ; Silvia Giliani^d ; Dale T. Umetsu^a ; Luigi D. Notarangelo^a ; ^g ; ¹ ; Raif S. Geha^a ; ¹
• 关键词：XLP ; X-linked lymphoproliferative disease ; SAP ; SLAM-associated protein ; EBV ; Epstein Barr Virus
• 刊名：Clinical Immunology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：146
• 期：2
• 页码：84-89
• 全文大小：591 K

文摘

X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency syndrome associated with the inability to control Epstein-Barr virus (EBV), lymphoma, and hypogammaglobulinemia. XLP is caused by mutations in the SH2D1A gene, which encodes the SLAM-associated protein (SAP), or in the BIRC4 gene, which encodes the X-linked inhibitor of apoptosis protein (XIAP).

Here we report a patient with recurrent respiratory tract infections and early onset agammaglobulinemia who carried a unique disease-causing intronic loss-of-function mutation in SH2D1A. The intronic mutation affected SH2D1A gene transcription but not mRNA splicing, and led to markedly reduced level of SAP protein. Despite undetectable serum immunoglobulins, the patient's B cells replicated and differentiated into antibody producing cells normally in vitro.