4例遗传性球形红细胞增多症患者的临床及遗传学分析

4例遗传性球形红细胞增多症患儿（男、女各2例），年龄3岁7个月至5岁，均有轻中度贫血、轻度肝脾肿大，以及间接胆红素增高为主的黄疸、网织红细胞比例增高、外周血涂片球形红细胞 > 10%和渗透性脆性增加。高通量测序分析发现病例1、2的SLC4A1基因分别存在新突变：c.37G > A和c.340T > C，其父母该基因均未见异常。c.37G > A和c.340T > C突变经Mutation Taster预测有致病意义；Polyphen2预测值分别为0.87、0.83，提示可能有害；SIFT的预测值分别为0.008、0.09，提示可能有害。病例3、4的ANK1基因分别存在已报道的c.830A > G和c.985G > C杂合突变；病例3的父母未做基因检测；病例4的母亲为遗传性球形红细胞增多症患者，也检出ANK1基因c.985G > C杂合突变。病例3的Hb常低于80 g/L，于5岁6个月行脾切除术，术后定期复查Hb均大于105 g/L。HS是一种由于红细胞膜蛋白异常导致的遗传性溶血性疾病，基因检测可协助确诊。

Clinical and genetic features of children with hereditary spherocytosis: an analysis of 4 cases

Four children (two boys and two girls), aged from 3 years and 7 months to 5 years, had mild or moderate anemia, mild hepatosplenomegaly, jaundice (mainly an increase in indirect bilirubin), an increase in the percentages of reticulocytes and spherical erythrocytes in peripheral blood smear and an increase in erythrocyte osmotic brittleness. High-throughput sequencing found two novel mutations in the SLC4A1 gene, c.37G > A and c.340T > C, in case 1 and case 2 respectively, and these two mutations were predicted to be pathogenic by Mutation Taster. The Polyphen2 scores of these two mutations were 0.87 and 0.83 respectively, which suggested that these mutations were probably damaging. The SIFT scores of these two mutations were 0.008 and 0.09 respectively, suggesting that these mutations were probably damaging. No abnormality in this gene was found in their parents. Two reported heterozygous mutations in the ANK1 gene, c.830A > G and c.985G > C, were found in case 3 and case 4 respectively. Gene detection was not performed for the parents of case 3. The mother of case 4 was diagnosed with hereditary spherocytosis and had a heterozygous mutation of c.985G > C in the ANK1 gene. All four children were diagnosed with hereditary spherocytosis. Case 3 had a hemoglobin level of < 80 g/L and underwent splenectomy at the age of 5 years and 6 months, and regular postoperative reexamination showed a hemoglobin level of > 105 g/L. Hereditary spherocytosis is a hereditary hemolytic disease caused by abnormality in erythrocyte membrane protein, and gene detection helps to make a confirmed diagnosis.