1例儿童先天性粒细胞减少症的基因诊断

Genetic diagnosis of a child with congenital neutropenia

目的应用基因诊断方法进一步提高对儿童先天性粒细胞减少症(CN)的认识和诊断水平。方法以1例儿童CN患者为研究对象,收集其临床资料、实验室检查结果,按序检测ELA2、GFI1、HAX1及WASp致病基因突变情况。依上述步骤对患儿分别进行疾病的临床及基因诊断并随访。结果参照诊断标准该患儿诊断为无遗传背景的散发性非综合征性CN;基因检测显示其携带已经报道的ELA2基因突变:c.164G>A;此外患儿中性粒细胞表面G-CSFR表达正常,G-CSFR胞内段未发现获得性截短性突变。结论基因突变检测证实1例儿童CN为ELA2基因突变所致,为该患儿未来的分组临床研究及基因治疗提供依据。

Objective To improve the understanding and diagnosis of congenital neutropenia （CN） in children by the use of gene mutation analysis. Methods Clinical data and laboratory results of a child suspected of CN were collected. ELA2, GFI1, HAX1, and WASp genes were sequenced. Clinical and genetic diagnosis of the child was made according to the above steps and a follow-up was carried out. Results The diagnosis ofa non-syndromic and sporadic CN with no genetic background was made for this patient according to the criteria; the mutation of c.164G〉A, p.Cys26Tyr in ELA2 which has been reported was found. Expression level of G-CSFR on the neutorphil from this patient was detected to be normal and no truncated mutation was found in the intracellular domain of G-CSFR. Conclusions The gene mutation analysis was performed for the genetic diagnosis of a child suspected of congenital neutropenia and ELA2 mutation of c.164G〉A, p.Cys26Tyr was confirmed in this case. The data provide the background for further clinical research as well as gene therapy in this patient.