CAJ | 학술논문

目的：总结2例中性粒细胞弹性蛋白酶（ ELANE）基因突变的先天性粒细胞减少症患儿的临床特征、基因诊断及治疗方法，提高对该病的认识。方法分析2例先天性粒细胞减少症患儿的临床表现，外周血中性粒细胞绝对计数（ ANC）变化，中性粒细胞呼吸爆发功能及其体液、细胞免疫功能，对ELANE基因5个外显子及外显子相邻区域进行直接测序，分析突变位点，探讨其治疗方法。结果①例1生后3个月反复肺部感染，例2生后1个月反复规律性口腔黏膜溃疡。②2例外周血ANC持续低于1.5×109·L-1，例1最低为0.01×109·L-1，例2最低为0.09×109·L-1，2例均排除感染、自身免疫性疾病及血液系统疾病。免疫功能评价：2例中性粒细胞呼吸爆发功能均正常，IgG升高，细胞免疫功能正常。③血ELANE基因分析发现：例1存在 c.661G ＞GT（ p. G221GX）杂合无义突变，其父母基因检测未发现突变。例2存在c.377C＞CT（p. S126SL）杂合错义突变，其胞姐和父母基因检测未发现突变。2个突变位点均为国内首次报道的已知致病突变，例1和2确诊年龄分别为3.25岁和13.5岁。④治疗：例2接受同胞造血干细胞移植成功，术后ELANE基因检测未发现突变，免疫重建成功；例1接受粒细胞集落刺激因子治疗。目前2例均在随访中。结论 ELANE基因是先天性粒细胞减少症的重要致病基因，造血干细胞移植是先天性粒细胞减少症的有效根治手段。
목적：총결2례중성립세포탄성단백매（ ELANE）기인돌변적선천성립세포감소증환인적림상특정、기인진단급치료방법，제고대해병적인식。방법분석2례선천성립세포감소증환인적림상표현，외주혈중성립세포절대계수（ ANC）변화，중성립세포호흡폭발공능급기체액、세포면역공능，대ELANE기인5개외현자급외현자상린구역진행직접측서，분석돌변위점，탐토기치료방법。결과①례1생후3개월반복폐부감염，례2생후1개월반복규률성구강점막궤양。②2예외주혈ANC지속저우1.5×109·L-1，례1최저위0.01×109·L-1，례2최저위0.09×109·L-1，2례균배제감염、자신면역성질병급혈액계통질병。면역공능평개：2례중성립세포호흡폭발공능균정상，IgG승고，세포면역공능정상。③혈ELANE기인분석발현：례1존재 c.661G ＞GT（ p. G221GX）잡합무의돌변，기부모기인검측미발현돌변。례2존재c.377C＞CT（p. S126SL）잡합착의돌변，기포저화부모기인검측미발현돌변。2개돌변위점균위국내수차보도적이지치병돌변，례1화2학진년령분별위3.25세화13.5세。④치료：례2접수동포조혈간세포이식성공，술후ELANE기인검측미발현돌변，면역중건성공；례1접수립세포집락자격인자치료。목전2례균재수방중。결론 ELANE기인시선천성립세포감소증적중요치병기인，조혈간세포이식시선천성립세포감소증적유효근치수단。
Objective To identify ELANE gene mutations in 2 Chinese cases with congenital neutropenia and to better understand the clinical characters,diagnosis and treatment of this rare disease. Methods Clinical data of the two cases with congenital neutropenia were collected,including clinical manifestations,trends of the absolute neutrophil count( ANC ),and immunological function. All 5 exons and flanking regions of ELANE gene were sequenced for the two cases and their families. Results Two cases were diagnosed as neutropenia at the age of 3 months and 1 month respectively,characterized with recurrent infections,including recurrent pneumonia in one case and oral mucosa ulcer in the other. Two cases presented with persistent neutropenia with the ANC less than 1. 5 × 109 ·L-1 ,the lowest ANC reached 0. 01 × 109 ·L-1 for case 1 and 0. 09 × 109 ·L-1 for case 2,respectively. Screening of blood serum and bone marrow was performed to exclude pathogenic infection,autoimmune disease and hematological malignancies. The respiratory burst of neutrophils and cellular immune function of both cases were normal,except for the elevated serum IgG level. Case 1 had c. 661G>GT(p. G221GX)heterozygous nonsense mutation in ELANE gene,case 2 had c. 377C>CT(p. S126SL)heterozygous missense mutation. No mutation was found in their family members. Case 2 received hematopoietic stem cell transplantation( HSCT)and presented with normal ELANE gene afterwards,case 1 was treated with G-CSF,both were followed up. Conclusion ELANE gene is the critical pathogenic gene for congenital neutropenia. HSCT is the effective radical treatment for this rare disease.