X-连锁淋巴细胞异常增生症一个中国人家系的临床和基因研究  

Clinical and gene research of X-linked lymphoproliferative disease in a Chinese family

作　　者：朱德新[1] 杜江[1] 兰和魁[1] 余力[1] 封志纯[1] 

机构地区：[1]南方医科大学附属珠江医院儿科,解放军421医院儿科510280

出　　处：《中华医学杂志》2007年第4期244-248,共5页National Medical Journal of China

摘　　要：目的证实中国人 X-连锁淋巴细胞异常增生症(XLP)发病及其遗传规律。方法临床研究对象为先证者双亲家族三代成员共14人;回顾分析其中发病者的住院病史;现场询问无病者的生长发育史、既往史,进行体格检查,并建卡追踪。基因研究对象为先证者同胞姐姐、弟弟和双亲共4人,提取单个核淋巴细胞基因组 DNA,PCR 扩增获得 SH2D1A 基因片段,单链构象多态性分析(SSCP)检测获得发生突变的外显子片段,纯化后测序,检测基因突变情况。结果先证者及其胞兄发生伴病毒相关性噬血细胞综合征(VAHS)的致死性传染性单核细胞增多症(IM),均于病程40 d 左右死亡。基因分析结果显示:先证者之胞弟 SH2D1A 基因 cDNA 第462位核苷酸 C 碱基突变为 T 碱基,形成终止密码 TGA,随后临床确诊为朗格罕细胞组织细胞增多症(LCH)。先证者之母亲在SH2D1A 基因同样部位为 C 碱基和 T 碱基的杂合子。先证者之父和胞姐未发现 SH2D1A 基因突变,他们及其家族其他成员无类似病史。结论 (1)先证者及其胞兄弟可临床诊断为 XLP 患者。(2)先证者之胞弟可明确诊断为 XLP 患者,LCH 可能也是 XLP 的一种新的临床表型。(3)先证者之母亲为突变基因的携带者。此家族 XLP 发病符合 X 性连锁隐性遗传规律。(4)本研究建立的 SH2D1A 基因检测分析方法可适用于我国 XLP 的诊治和研究。Objective To verify the pathogenesis in Chinese and to investigate the genetic rule of X-linked lymphoproliferative disease （XLP） therein. Methods The case history of a proband of XLP, male, aged 1 year and 5 months, who died 40 days after hospitalization, was reviewed. Fourteen his family members were interviewed for the development history, anamnesis, and underwent physical examination. Single-strand conformation polymorphism （SSCP-PCR） and sequencing were used to detect the SH2D1A mutation among the elder sister, younger brother, and parents of the poband. Results The proband and his elder brother suffered with virus-associated hemophagocytic syndrome and both died in 40 days after the disease coming on in the last two years in succession. The second exon of SH2D1A of the younger brother of the proband showed a nonsense mutation in SH2D1A gene： the C-T nucleotide substitution at nucleotide position 462 result in a stop codon and pre-mature termination of protein synthesis. The mother was proved as mutation heterozygote of the C and T nucleotide on the same site. The other members of the family were proved normal. The clinical manifestation of the younger brother of the proband was Langehans cell histiocytosis. Conclusion Langehans cell histiocytosis may be a new clinical phenotype of XLP. The gene of SH2D1A is responsible for the disease of XLP in Chinese too. The newly developed method of SH2D1A mutation analysis may be suitable in the diagnosis of XLP in Chinese.

关 键 词：淋巴组织增殖性疾病 爱泼斯坦巴尔病毒感染 SH2D1A基因 

分 类 号：R55[医药卫生—血液循环系统疾病]