Wang Xiong, Zhang Ai, Huang Ming, Chen Li, Hu Qun, Lu Yanjun, Cheng Liming
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2020 Aug 18;11:953. doi: 10.3389/fgene.2020.00953. eCollection 2020.
Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes (, , , , and ). We investigated molecular spectrum and genotype-phenotype correlation in HS patients in Hubei province, central China. Twenty-three patients with HS were included. A next-generation sequencing (NGS) panel targeting , , , , and genes was used to screen potential variants. Sanger sequencing was applied to validate variants. Of the twenty-three patients, thirteen patients carried variants, and ten patients harbored variants, including ten non-sense, six indel, four splice site, one start-loss, and one missense variant. Four out of twenty-two variants in our study were known, and eighteen variants were novel. Most and variants were indel (5/12) or non-sense (7/10), respectively. Family member analysis in thirteen families showed that six variants were . Variable expressivities were observed in a pair of twins with c.341C > T variant, and two unrelated patients both carried c.2T > A variant. Genotype-phenotype analysis found no significant difference between and regarding the levels of Hb, RBC, MCV, MCH, and MCHC. However, variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains. In conclusion, NGS is a fast way to provide a molecular HS diagnosis. We also identified unique genetic and clinical characteristics of patients with HS in Hubei Province, China. However, a large sample size is needed to further investigate the genotype-phenotype correlation.
遗传性球形红细胞增多症（HS）是一种遗传性疾病，其特征为贫血、脾肿大和球形红细胞，由红细胞膜蛋白基因（ 、 、 、 和 ）突变引起。我们对中国中部湖北省HS患者的分子谱及基因型 - 表型相关性进行了研究。纳入了23例HS患者。使用针对 、 、 、 和 基因的二代测序（NGS）面板筛选潜在变异。应用桑格测序验证变异。在这23例患者中，13例患者携带 变异，10例患者携带 变异，包括10个无义变异、6个插入缺失变异、4个剪接位点变异、1个起始密码子缺失变异和1个错义变异。我们研究中的22个变异中有4个是已知的，18个变异是新发现的。大多数 变异和 变异分别为插入缺失（5/12）或无义变异（7/10）。对13个家庭的家庭成员分析显示，6个变异为 。在一对携带 c.341C > T变异的双胞胎中观察到可变表达，并且两名无关患者均携带 c.2T > A变异。基因型 - 表型分析发现，在血红蛋白（Hb）、红细胞（RBC）、平均红细胞体积（MCV）、平均红细胞血红蛋白含量（MCH）和平均红细胞血红蛋白浓度（MCHC）水平方面， 和 之间无显著差异。然而，与ANK1其他结构域相比，ANK1死亡结构域中的变异与较低的MCV和MCH水平相关。总之，NGS是提供HS分子诊断的快速方法。我们还确定了中国湖北省HS患者独特的遗传和临床特征。然而，需要大样本量来进一步研究基因型 - 表型相关性。
