中文摘要：

目的研究一个伴有红细胞和血小板异常的植物固醇血症家系的临床、生物化学和分子生物学特征。方法用高效液相色谱方法检测血浆植物固醇含量；PCR法扩增ABCG5和ABCG8基因的所有外显子和侧翼序列，DNA测序确定基因异常，限制性内切酶（Bfa I）分析该家系及70名正常人相应序列的PCR产物。结果3例患者临床主要表现为溶血和巨大血小板，其血浆谷固醇、豆固醇和二氢胆固醇浓度明显增高而总胆固醇浓度正常。发现在ABCG5基因外显子l中18802位碱基发生C→T突变，导致22位的谷氨酸（Q）变为终止密码子。3例患者均为纯合子，其父母及两个亲属为杂合子。ABCG8基因测序结果未见异常。限制性内切酶Bfa1分析70名正常人相应序列的PCR产物未发现相同的基因突变。结论血细胞是血浆植物固醇毒性作用的一个靶子，红细胞和血小板的异常是植物固醇血症的一种特殊的表型。

英文摘要：

Objective To investigate the clinical, biochemical and molecular genetic features of a family with sitosterolemia coexisting erythrocyte and platelet abnormalities. Methods The clinical features of the affected patients were analysed. Plasma sterol levels were measured by HPLC. All the exons and exon-intron boundaries of the ABCG5 and ABCG8 genes were amplified by PCR and then DNA sequencing. Restriction endonuclease analysis （REA） was used for the PCR products of the family members and 70 non-related healthy volunteers. Results The main clinical feature of the three affected patients was hemolysis, macrothrombocytes increased plasma sitosterol, stigmasterol and cholestanol levels but normal cholesterol levels. Sequence analysis of ABCG5 and ABCG8 genes revealed a C to T transition at nucleotide 18 802 resulting in a nonsense mutation in ABCG5 exon 1, Gln22X, whereas no defects were found in ABCG8 gene. The affected patients were homozygous while their parents and two other family members were heterozygous for this defect. Allele-specific REA using Bfa I showed that this mutation was not detected in 70 healthy subjects. Conclu- sion The blood cells could be a ＂target＂ for the toxic effect of plasma phytosterols, and the coexisting hematological abnormalities might represent a specific subtype of sitosterolemia. A novel nonsense mutation in ABCG5 gene was reported.