在中性粒细胞减少症患儿中筛查 ELANE、HAX1 和 GFI1 基因突变及 ELANE 基因突变的两种新突变的临床特征。
Screening for ELANE, HAX1 and GFI1 gene mutations in children with neutropenia and clinical characterization of two novel mutations in ELANE gene.
机构信息
Departments of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Department of Pediatrics, Hatyai Hospital, Hatyai, Songkhla, Thailand.
出版信息
BMC Pediatr. 2023 Nov 23;23(1):592. doi: 10.1186/s12887-023-04428-w.
BACKGROUND
Congenital neutropenia is a rare disease. Recurrent infections since young age are the presentation. The most common mutation causing severe congenital neutropenia (SCN) and cyclic neutropenia (CyN) is the ELANE gene. The objectives of this study were to screen the three common genetic mutations of ELANE, HAX1 and GFI1 in children with chronic neutropenia and to describe the clinical characteristics of children who had the mutations.
METHODS
Infants having ANC < 1,000/cu mm or children aged > 1 year having ANC < 1,500/cu mm at least 3 times in 3 months were enrolled in the study. Patients who had acquired neutropenia due to infection, immune deficiency, or drugs were excluded. The ELANE gene was first studied; and if mutations were not identified, the HAX1 and GFI1 genes were further examined.
RESULTS
A total of 60 patients were enrolled in the study. The median (range) age, ratio of female to male, ANC, and last follow-up age were 9.2 (0.5-45.2) months, 1:1.2, 248 (0-1,101) /cu mm, and 19.9 (3.5-202.3) months, respectively. Infections were noted in 67.3% of all patients. ELANE gene mutation was found in only four patients (6.7%), and the rest (56 patients) showed no mutations in the HAX1 and GFI1 genes. In patients without mutations, 66.0% had normal ANC during the follow-up, with a median (range) age for normal ANC of 19.8 (4.0-60.0) months. Two novel mutations p. Ala79del (c.234_236del) and p. Val197GlufsTer18 (c.589_590insAGGCCGGC) were identified, and they respectively cause SCN and CyN. Patients with the two novel mutations presented with several episodes of infection, including pneumonia, sepsis, abscess, otitis media, and gum infection.
CONCLUSION
The genetic screening for ELANE, HAX1, and GFI1 gene mutations in 60 patients with chronic neutropenia could identify four patients (6.7%) with ELANE gene mutation and two novel mutations, p. Ala79del in exon 3 and p. Val197GlufsTer18 in exon 4 causing SCN; and CyN, respectively.
背景
先天性中性粒细胞减少症是一种罕见的疾病。其特征是年轻时反复发生感染。导致严重先天性中性粒细胞减少症（SCN）和循环中性粒细胞减少症（CyN）的最常见突变是 ELANE 基因。本研究的目的是筛查儿童慢性中性粒细胞减少症中 ELANE、HAX1 和 GFI1 的三种常见基因突变，并描述具有突变的儿童的临床特征。
方法
ANC<1000/cu mm 的婴儿或年龄>1 岁且 ANC<1500/cu mm 的儿童，至少在 3 个月内发生 3 次，应纳入本研究。因感染、免疫缺陷或药物而获得中性粒细胞减少的患者被排除在外。首先研究 ELANE 基因；如果未发现突变，则进一步检查 HAX1 和 GFI1 基因。
结果
共纳入 60 例患者。中位（范围）年龄、男女比例、ANC 和最后随访年龄分别为 9.2（0.5-45.2）个月、1:1.2、248（0-1101）/cu mm 和 19.9（3.5-202.3）个月。所有患者中，67.3%有感染。仅在 4 例患者（6.7%）中发现 ELANE 基因突变，其余（56 例）在 HAX1 和 GFI1 基因中未发现突变。在无突变的患者中，66.0%的 ANC 在随访期间正常，ANC 正常的中位（范围）年龄为 19.8（4.0-60.0）个月。发现了两种新突变 p.Ala79del（c.234_236del）和 p.Val197GlufsTer18（c.589_590insAGGCCGGC），它们分别导致 SCN 和 CyN。具有这两种新突变的患者出现了多次感染，包括肺炎、败血症、脓肿、中耳炎和牙龈感染。
结论
对 60 例慢性中性粒细胞减少症患者的 ELANE、HAX1 和 GFI1 基因突变进行基因筛查，可发现 4 例（6.7%）ELANE 基因突变和 2 种新突变，第 3 外显子 p.Ala79del 和第 4 外显子 p.Val197GlufsTer18 分别导致 SCN 和 CyN。
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