Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67^phox result in autosomal recessive CGD. We describe three patients with a novel c.855G>C NCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8–9 duplication, while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67^phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically, the homozygous patient presented with suspected early onset interstitial lung disease and NCF2 mutation was found on genetic testing performed in search for surfactant-related defects. The two siblings also had variable presentation with one having history of severe pneumonia, lymphadenitis, and recurrent skin abscesses and the other presenting in his 30s with discoid lupus erythematosus and without significant infectious history. We therefore identified a novel pathogenic NCF2 mutation causing diverse and unusual clinical phenotype.

慢性肉芽肿病 (CGD) 是一种罕见的原发性免疫缺陷病，由 NADPH 氧化酶复合物缺陷引起。编码胞质因子p67 ^{phox 的}NCF2突变导致常染色体隐性 CGD。我们描述了三名具有新的 c.855G>C NCF2突变的患者，这些突变呈现出不同的临床表型。两个兄弟姐妹对于新突变和先前描述的外显子 8-9 重复是杂合的，而第三个无关患者对于新突变是纯合的。突变的致病性通过异常的 DHR123 测定和 p67 ^{phox 的}缺失得到证实生产和测序显示异常 RNA 剪接的 cDNA。临床上，纯合子患者疑似早发性间质性肺病，在寻找表面活性剂相关缺陷的基因检测中发现NCF2突变。这两个兄弟姐妹也有不同的表现，一个有严重的肺炎、淋巴结炎和复发性皮肤脓肿病史，另一个在 30 多岁患有盘状红斑狼疮，没有明显的感染史。因此，我们确定了一种新的致病性NCF2突变，该突变导致多种不同寻常的临床表型。