37例遗传性球形细胞增多症基因突变特征分析

The characteristic of hereditary spherocytosis related gene mutation in 37 Chinese hereditary spherocytisis patients

目的揭示遗传性球形细胞增多症（HS）红细胞膜蛋白基因突变特征。 方法应用二代测序技术检测2015年4月至2018年1月临床明确诊断的51例HS患者红细胞膜蛋白基因突变情况，将检出并预测为红细胞膜蛋白基因有害突变的37例患者纳入研究，分析基因突变构成、突变类型及与临床表现型的关系。 结果37例HS患者中，ANK1突变17例（45.9%）、SPTB突变14例（37.8%）、SLC4A1突变5例（13.5%）、ANK1突变复合SPTB突变1例（2.7%），未发现SPTA1及EPB42突变。红细胞膜蛋白基因突变类型中无义突变（36.8%）和错义突变（31.6%）最常见。在检出的38个突变位点中，34个为新发突变（89.5%）。16例HS患者进行父母基因验证，6例（37.5%）为遗传获得突变，10例（62.5%）为自发突变。HS患者外周血细胞参数与红细胞膜蛋白突变基因类型无关；轻型＋中间型患者SPTB突变构成比更高，重型患者ANK1突变构成比更高，但差异无统计学意义（P=0.664）。 结论中国HS以ANK1和SPTB基因突变最常见，突变类型主要为错义突变和无义突变；不同HS相关基因突变与HS严重程度间无明显相关。

ObjectiveTo reveal the genetic characteristics of erythrocyte membrane protein in hereditary spherocytosis （HS） in China.MethodsNext-generation sequencing technology was used to detect mutations in genes of erythrocyte membrane proteins in 51 clinically diagnosed HS patients. The relationship between gene mutations and clinical phenotypes was analyzed.ResultsMutations in erythrocyte membrane protein genes were detected in 37 patients, including 17 with ANK1 mutations （17/37, 45.9%）, 14 with SPTB mutations （14/37, 37.8%）, and 5 with SLC4A1 mutations （5/37, 13.5%）. One patient carried both heterozygous ANK1 mutation and SPTB mutation （1/37, 2.7%）. SPTA1 and EPB42 mutation was not fou nd in any patient. Nonsense mutations （36.8%） and missense mutations （31.6%） were most common. Of the 38 mutations detected, 34 were novel mutations and have not been reported elsewhere （89.5%）. Sixteen HS patients underwent parental genetic validation, 6 patients （37.5%） inherited gene mutation from parents and 10 （62.5%） were de novo. The peripheral blood cell parameters of HS patients were not related to the mutant genes and gene mutation types. However, it seems that HS patients with mild clinical status are prone to carry SPTB mutations while more patients with severe clinical status have ANK1 mutations.ConclusionsANK1 and SPTB are the most common mutant genes in Chinese HS patients, mainly with missense mutations and nonsense mutations. There was no significant correlation between the mutation of HS related genes and the severity of HS.