戈谢病GBA基因突变致血小板输注无效1例

摘要

Objective To analyze the mutation characteristics of GBA gene in one patient with Gaucher disease and platelet transfusion refractoriness.Methods A female patient with anemia and thrombocytopenia showed platelet transfusion refractoriness,and then the proband and her family were performed bone marrow smear,β-glucocerebrosidase activity in leukocytes (dried blood spot assay),Bultrasonography and gene sequencing examination and pedigree investigation.Results Pedigree investigation showed that the heterozygous mutation of GBA gene existed in the father,mother,son,daughter and sister of the proband.Bone marrow cytomorphologic examination showed that Gaucher cells accounted for 6.0％ in the female patient.The β-glucocerebrosidase activity in leukocytes was 3.78 nmol/(h · mg Pro).B-ultrasonography showed slightly splenomegaly.Gene sequencing found that the homozygous mutation of GBA gene,c.484A ＞ G,existed in the female patient.Conclusion The patients with Gaucher disease may appear platelet transfusion refractoriness due to hypersplenism.The mutation of GBA gene is the main pathogenic factor of the family with Gaucher disease.%目的 分析1例血小板输注无效患者及其家系戈谢病葡萄糖脑苷脂酶(GBA)基因突变特征.方法 1例贫血及血小板减少的女性患者经血小板输注无效后,对其进行骨髓细胞学、B超及基因测序检测;采用干血斑法检测其白细胞β-葡糖脑苷脂酶活性;提取该家系8个成员(包括先证者及其直系亲属)外周血基因组DNA进行基因测序.结果 骨髓细胞学检查示该例患者可见戈谢细胞(6.0％),白细胞β-葡糖脑苷脂酶活性为3.78 nmol/(h·mgPro),B超结果示脾肿大;基因测序分析发现其为GBA基因c.484A＞G纯合错义突变;家系调查结果表明,先证者父母、子女及妹妹5人均为GBA基因杂合突变.结论 戈谢病患者可因脾功能亢进而出现血小板输注无效;GBA基因突变为该家系的主要致病因素.