Correlation of mutations of the SH2D1A gene and Epstein-Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease

作     者：Sumegi, J Huang, DL Lanyi, A Davis, JD Seemayer, TA Maeda, A Klein, G Seri, M Wakiguchi, H Purtilo, DT Gross, TG 

作者机构：Univ Nebraska Nebraska Med Ctr 985454 Dept Pathol & MicrobiolCtr Human Mol Genet Eppley Inst Res Canc & Allied Dis Omaha NE 68198 USA Univ Nebraska Med Ctr Dept Pathol & Microbiol Omaha NE 68198 USA Univ Nebraska Med Ctr Dept Pediat Omaha NE 68198 USA Karolinska Inst Ctr Microbiol & Tumorbiol Stockholm Sweden Inst Giannina Gaslini Mol Genet Lab Genoa Italy Kochi Med Sch Dept Pediat Nankoku Kochi Japan Childrens Hosp Med Ctr Div Hematol & Oncol Cincinnati OH 45229 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第9期

页      面：3118-3125页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NIAID NIH HHS [1RO1AI33532-OIA3] Funding Source: Medline 

主　　题：选择性剪接 氨基酸序列 载体蛋白质类/遗传学 染色体图 爱泼斯坦巴尔病毒感染/并发症 外显子 遗传标记 细胞内信号肽和蛋白质类 内含子 淋巴组织增殖性疾病/遗传学 淋巴组织增殖性疾病/病毒学 分子序列数据 突变 突变 误义 系谱 表型 多态性 限制性片段长度 试验预期值 预后 逆转录聚合酶链反应 序列比对 序列缺失 序列同源性 氨基酸 X染色体 src同源域 女(雌)性 人类 男(雄)性 

摘      要：The purposes of this study were to determine the frequency of mutations in SH2D1A in X-linked lymphoproliferative disease (XLP) and the role of SH2D1A mutations and Epstein-Barr virus (EBV) infection in determining the phenotype and outcome of patients with XLP. Analysis of 35 families from the XLP Registry revealed 28 different mutations in 34 families-large genomic deletions (n = 3), small intragenic deletions(n = 10), splice-site (n = 3), nonsense (n = 3), and missense (n = 9) mutations. No mutations were found in 25 males, so-called sporadic XLP (males with an XLP phenotype after EBV infection but no family history of XLP) or in 9 patients with chronic active EBV syndrome. Of 304 symptomatic males in the XLP Registry, 38 had no evidence of EBV infection at first clinical manifestation, When fulminant infectious mononucleosis (FIM) was excluded, there was no statistical difference in the frequency of EBV infectivity In the other XLP phenotypes. Furthermore, there was no difference at age of first clinical manifestation between EBV+ and EBV- males or in survival when patients with FIM were excluded. In conclusion, it was found that mutations in the SH2D1A gene are responsible for XLP but that there is no correlation between genotype and phenotype or outcome. It was also found that though EBV infection often results in FIM, it is unnecessary for the expression of other manifestations of XLP, and it correlates poorly with outcome. These results suggest that unidentified factors, either environmental or genetic (eg, modifier genes), contribute to the pathogenesis of XLP. (C) 2000 by The American Society ct Hematology.