三个伴有巨大血小板和溶血性贫血的植物固醇血症家系研究  

Clinical and gene study of three pedigrees of phytosterolemia associated with macrothrombocytopenia and hemolysis

作　　者：王改锋[1] 王兆钺[1] 曹丽娟[1] 江明华[1] 孙雄华[1] 白霞[1] 阮长耿[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,卫生部血栓与止血重点实验室,215006

出　　处：《中华血液学杂志》2011年第5期331-336,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81070395）

摘　　要：目的研究3个以血液学改变为首发临床表现的植物固醇血症先证者及家系的临床表型和基因诊断。方法光学显微镜观察红细胞及血小板的形态；高效液相色谱法检测血浆中豆固醇、二氢胆固醇及谷固醇的含量；PCR法扩增先证者ABCG5和ABCG8基因外显子和侧翼序列，针对先证者的突变位点，对其家系成员进行相应片段基因的检测；同时在正常人群中筛查以排除多态性。结果巨大血小板、溶血性贫血、脾脏肿大及黄褐瘤是患者共同的表现。外周血涂片可见异形红细胞，如口形红细胞增多，血小板体积增大甚至达红细胞大小；血浆中植物固醇尤其是谷固醇的含量显著增高，是正常人30倍左右；基因分析发现4个突变：ABCG5C20896T（R446X）、A20883G，ABCG8del43683-43724、del43866C-43867G／ins43866T，后3个是新的突变位点。结论伴有巨大血小板和溶血性贫血的植物固醇血症是植物固醇血症一个特殊的亚型。对不能解释的巨大血小板，尤其是伴有溶血或（和）口形红细胞的患者应考虑植物固醇血症的可能。Objective To study the clinical features and ABCGS/ABCG8 gene mutations of three pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis. Methods Erythrocyte and platelet morphology were examined under light microscope. Plasma sterol levels were measured by high pressure/performance liquid chromatography method. All of ABCG5 and ABCG8 exous and intron-exon boundaries were directly sequenced to identify mutations, the corresponding gene mutation sites of three families members and healthy individuals were detected. Results All the patients presented macrothrombocytopenia, hemolysis, splenomegaly and xanthomas. The blood smears showed large platelets, some as large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes. Plasma concentrations of phytosterols, especially sitosterol were markedly elevated （30 fold） in the affected patients. Four mutations were identified in these three pedigrees, ABCG5 C20896T （R446X） and A20883G , ABCG8 de143683-43724 and del1938C-1939G/ins1938T. The latter three were novel mutations reported for the first time. Conclusions Phytosterolemia associated with macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma phytosterols and related gene analysis should be performed when ever an unexplained macrothrombocytopeuia, especially combined with haemolysis or/and stomatocytosis.

关 键 词：血小板减少症 贫血 溶血性 植物固醇血症 DNA突变分析 

分 类 号：R440[医药卫生—诊断学]