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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 confirm the pathogenesis of Chinese X-linked lymphocytic dysplasia (XLP) and its hereditary rules. Methods The clinical research subjects were probands, two parents and three generations of family members, 14 persons in total. The hospitalized patients were reviewed retrospectively. The patients were asked about their growth and development history, past history, physical examination and card tracing. Genes for the proband siblings siblings, brother and parents a total of 4 people, extracted from a single nuclear lymphocyte genomic DNA, PCR amplification of SH2D1A gene fragment, single-strand conformational polymorphism analysis (SSCP) detected mutations were detected Sub-fragment, purified after sequencing, detection of gene mutations. Results The proband and his brother developed deadly infectious mononucleosis (IM) with virus-associated hemophagocytic syndrome (VAHS), both of which died within about 40 days. The result of gene analysis showed that the 462 nucleotides C base of cDNA of SH2D1A gene of the proband were mutated to T base to form a stop codon TGA, and subsequently diagnosed as Langerhans cell histiocytosis (LCH). The proband’s mother is heterozygote of C base and T base in the same site of SH2D1A gene. The father and sister did not find SH2D1A gene mutation, they and other members of their family have no similar history. Conclusion (1) The probands and their siblings can be clinically diagnosed as XLP patients. (2) The proband’s brother can be clearly diagnosed as XLP patients, LCH may also be a new clinical phenotype of XLP. (3) The mother of the proband is the carrier of the mutated gene. The incidence of this family line XLP X-linked recessive genetic law. (4) The SH2D1A gene detection and analysis method established in this study can be applied to the diagnosis and research of XLP in our country.