51例先天性中性粒细胞减少症患者临床特点与基因突变分析

Clinical characteristics and mutation analysis of 51 patients with congenital neutropenia

目的:探讨先天性中性粒细胞减少症(CN)患儿的临床特点与基因突变情况。方法:回顾性分析2006年1月—2020年12月我中心确诊的51例CN患儿临床特点,采用二代测序方法检测CN相关致病基因突变。结果:共入组51例CN患儿,男25例,女26例,中位发病年龄16个月(0~142个月),约79.54%的患儿有频繁感染病史,中位中性粒细胞计数0.30×10^(9)/L(0.07×10^(9)/L~0.88×10^(9)/L)。流式细胞术检测21例患儿淋巴细胞亚群,CN患儿CD3 T细胞和CD19 B细胞比例平均值低于同年龄段正常儿童。而CN儿童各年龄段IgG、IgA平均值略高于同年龄段正常儿童。完成基因测序的31例CN患儿中,15例检出CN相关基因突变,包括ELANE突变4例,CXCR4突变2例,GATA2、GFI1、G6PC3、HAX1、AP3B1、CSF3R、LYST、VPS13B各1例,另有1例患儿同时携带VPS45及AP3B1杂合突变。结论:CN患儿发病年龄小,多数有频繁感染病史,可能存在淋巴细胞亚群异常。ELANE为CN常见的致病突变。

Objective: To investigate the clinical characteristics and mutation of congenital neutropenia(CN). Methods: We retrospectively analyzed the clinical characteristics of 51 children with CN. Mutations of CN-related genes were detected by the second generation sequencing. Results: Totally 51 children with CN were involved, including 25 males and 26 females. The median age of onset was 16 months(0-142 months). About 79.54% of the children had a history of frequent infection. The median neutrophils count was 0.30×10^(9)/L(0.07×10^(9)/L-0.88×10^(9)/L). The percentages of CD3 T cells and CD19 B cells in 21 of the 51 children, detected by flow cytometry, were lower than those in the normal children. The mean IgG and IgA of children with CN were slightly higher than those of normal children. CN-related gene mutations were detected in 15 of the 31 CN children, including 4 cases of ELANE mutation, 2 cases of CXCR4 mutation, and 1 case each of GATA2, GFI1, G6 PC3, HAX1, AP3 B1, CSF3 R, LYST and VPS13 B. There was another case with both VPS45 and AP3 B1 heterozygous mutations. Conclusion: The onset age of CN children is young and most of them have a history of frequent infection. Abnormal lymphocyte subsets may present in CN. ELANE is the most common pathogenic mutated gene.