Sun Jinqiao, Wen Min, Wang Ying, Liu Danru, Ying Wenjing, Wang Xiaochuan
Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
BMC Med Genet. 2017 Nov 13;18(1):127. doi: 10.1186/s12881-017-0492-6.
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by the defect of NADPH oxidase. Mutations in CYBB or CYBA gene may result in membrane subunits, gp91phox or p22phox, expression failure respectively and NADPH oxidase deficiency. Previous study showed that three variants, c.214 T > C (rs4673), c.521 T > C (rs1049254) and c.24G > A (rs1049255), in CYBA gene form a haplotype, which are associated with decreased reactive oxygen species generation. The study aims to confirm the three above mentioned variants are benign and report a novel mutation in CYBB gene.
A patient with CGD and his family members were enrolled in the study. NADPH oxidase activity and gp91phox protein expression of neutrophils were analyzed by flow cytometry. Direct sequencing was used to detect CYBB and CYBA gene mutations.
The patient was diagnosed with CGD according to clinical and immune phenotype. The case has a novel homozygous mutation in CYBB gene and the above mentioned three variants in CYBA gene. The mutation in CYBB gene was confirmed to be pathogenic, and the three variants in CYBA gene to be benign.
The study not only reported a novel mutation in CYBB, which results in CGD, but also confirmed the above mentioned three variants in CYBA are benign.
慢性肉芽肿病（CGD）是一种由烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶缺陷引起的遗传性免疫缺陷病。CYBB或CYBA基因突变可能分别导致膜亚基gp91phox或p22phox表达失败以及NADPH氧化酶缺乏。先前的研究表明，CYBA基因中的三个变异体c.214 T＞C（rs4673）、c.521 T＞C（rs1049254）和c.24G＞A（rs1049255）形成一种单倍型，与活性氧生成减少相关。本研究旨在证实上述三个变异体为良性，并报告CYBB基因中的一个新突变。
一名CGD患者及其家庭成员被纳入本研究。通过流式细胞术分析中性粒细胞的NADPH氧化酶活性和gp91phox蛋白表达。采用直接测序法检测CYBB和CYBA基因突变。
根据临床和免疫表型，该患者被诊断为CGD。该病例在CYBB基因中有一个新的纯合突变，在CYBA基因中有上述三个变异体。CYBB基因中的突变被证实为致病性突变，CYBA基因中的三个变异体为良性变异体。
本研究不仅报告了一个导致CGD的CYBB新突变，还证实了CYBA基因中的上述三个变异体为良性变异体。
