NCF2基因复合杂合突变导致慢性肉芽肿病1例并文献复习

Chronic granulomatous disease caused by compound heterozygous mutation in NCF2 gene:case report and literature review

目的探讨NCF2基因复合杂合突变导致的儿童慢性肉芽肿病(CGD)突变类型与临床特征、预后之间的关系。方法分析2019年8月天津市儿童医院诊治的1例由NCF2基因复合杂合突变导致新生儿CGD的临床资料,并检索国内外文献,总结NCF2基因突变引起的CGD的临床特征、基因突变类型及预后等特点。结果该患儿NCF2基因上存在复合杂合突变c.196_197insA(p.Arg66Glnfs23X)和c.1180T>G(p.Tyr394Asp),结合出生25 d发热、咳嗽、胸CT肺部多发团块影、结节影的临床表现、中性粒细胞呼吸爆发试验刺激指数23,确诊CGD。此突变在人类基因突变数据库中未见报道,为新突变。该患儿残留一部分烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性,服用抗真菌药物随访至9月龄未出现反复感染。国内外数据库报道NCF2基因突变的CGD患者共101例。有中性粒细胞呼吸爆发试验刺激指数结果者共33例,3以下22例;3以上11例,其中含错义突变8例。结论c.196_197insA和c.1180T>G是NCF2基因的新突变,可导致CGD。含NCF2基因错义突变的CGD患者可能残留更多NADPH氧化酶活性。

Objective To explore the relationship between the type of mutation and clinical features,prognosis,and clinical characteristics of chronic granulomatous disease(CGD)caused by compound heterozygous mutations in the NCF2 gene in children.Methods The clinical data of 1 case of neonatal CGD caused by compound heterozygous mutations of NCF2 gene at Tianjin Children′s Hospital in August 2019 was analyzed,and domestic and international literatures were searched to summarize the clinical characteristics,gene mutation type and prognosis of CGD caused by NCF2 mutation.Results The diagnosis of CGD was confirmed by the presence of compound heterozygous mutations c.196_197insA(p.Arg66Glnfs23X)and c.1180T>G(p.Tyr394Asp)in the NCF2 gene,accompanied with the clinical manifestations of fever,cough,multiple clumps and nodules in the chest CT at 25 days after birth,and the neutrophil respiratory burst test stimulation index(SI)23.This new mutation was not reported in the Human Genetic Mutation Database.The child had a residual portion of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase activity and was followed up until the age of 9 months with an antifungal drug without recurrent infection.A total of 101 cases of CGD patients with NCF2 gene mutation were reported in domestic and international databases.Totally,33 cases had SI results,with 22 cases below 3,11 cases above 3,and 8 cases of missense mutations.Conclusions c.196_197insA and c.1180T>G are new mutations in NCF2 gene that can lead to CGD.CGD patients containing missense mutations in the NCF2 gene may have more residual NADPH oxidase activity.