X-连锁淋巴细胞异常增生症一例及其家系基因和蛋白表达研究  

Genetic and proteinic analysis of a Chinese boy with X-linked lymphoproliferative disease and his maternal relatives

作　　者：杨曦[1] 王晶[1] 安云飞[1] 金兼弘和 宫脇利男 赵晓东[1] 

机构地区：[1]重庆医科大学附属儿童医院P2实验室,400014 [2]日本富山大学医学部小儿科

出　　处：《中华儿科杂志》2011年第6期416-420,共5页Chinese Journal of Pediatrics

基　　金：重庆市杰出青年科学基金（CSTC,2008BA5040）

摘　　要：目的 探讨1例中国X-连锁淋巴细胞异常增生症（XLP）患儿及其家系的临床特征、基因突变和外周血单个核细胞（PBMC）SAP蛋白表达.方法 患儿男,6岁,于5岁时发现右腰部肿物,活检提示为伯基特淋巴瘤.其胞兄及表兄均于1岁左右因重症传染性单核细胞增多症夭折.据临床表现、家族史、免疫学特征拟诊为XLP.提取患儿及部分亲属基因组DNA,采用PCR法扩增SH2D1A基因,PCR产物直接进行双向序列测定,采用流式细胞仪检测PBMC中SAP蛋白表达.结果 患儿在缓解期EBV-DNA检测为536.9拷贝/ml（＞500拷贝/ml为EBV阳性）,其SH2D1A基因第2外显子462位核苷酸发生无义突变,碱基C突变为T,形成TGA终止密码子（Arg55X）,患儿母亲、姨母及外祖母为该突变携带者.患儿PBMC中SAP蛋白表达水平明显下降,而携带者SAP蛋白表达未见异常.结论 通过临床及实验室检查,确诊1例XLP患儿及家系.男性重症EBV感染,甚或无EB病毒感染证据,但具有家族史的淋巴瘤患儿应考虑XLP.SAP蛋白流式细胞仪检测为快速、准确的诊断手段.Objective X-linked lymphopmliferative disease（XLP）,a genetic disorder characterized by immunodeficiency to Epstein-Barr virus（EBV）infection,has been linked to mutations in the SH2D1 A gene.XLP patient displays EBV associated fulminant infectious mononucleosis or hemophagocytie lymphohistocytosis,hypogammaglobulinemia or malignant lymphoma.Here we report the clinical features.gene mutation and SAP expression on PBMCs of a Chinese patient with XLP and potential carriers.Method A 6 years old male patient and his maternal relatives were enrolled in this study.The patient was found to have with a renal Burkitt lymphoma on the right waist at 5 years of age by accident.His elder brother and a maternally related cousin botIl died of multiple systemic organ dysfunction syndrome （MODS）due to fulminant infectious mononucleosis（FIM）at the age of one year.The patient and his maternal relatives were subjected to detection of SAP expression on the PBMCs by flow cytometry and gene mutation analysis of SH2D1A by using PCR based on genomic DNA.Result The patient exhibited 536.9copy/ml level of circulating EBV-DNA during remission.Sequence analysis showed that the patient harbored a nonsense mutation in exon 2（C462T）,resulting in a premature stop codon（Arg55X）.His mother and some of the matemal relatives were proved to be carriers of this mutation.SAP expression from the patient was significantly reduced as compared to normal individual and the carriers.Conclusion We identified a Chinese XLP ease genetically.Assessment of SAP expression on PBMCs by flow cytometry seemed to be an effective rapid diagnostic method for this disease.Absence of EBV infeetion does not diminish the possibility of XLP.

关 键 词：淋巴组织增殖性疾病 伯基特淋巴瘤 SH2D1A 基因 突变 

分 类 号：R725.9[医药卫生—儿科]