Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

Purpose We aimed to report the clinical and immunological characteristics of variant type X91 + chronic granulomatous disease (CGD) in a Chinese cohort. Methods The clinical manifestations and immunological phenotypes of patients with X91 + CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91 phox protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry. Results Patients with X91 + CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91 + CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections. Mycobacterium tuberculosis infection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91 + CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91 + CGD, X91 − CGD, and X91 0 CGD) was statistically significant ( P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency. CYBB mutations associated with X91 + CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91 + CGD–related mutations (c.1462–2 A > T, c.1243C > T, and c.925G > A) were identified. Conclusions Variant type X91 + CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91 + CGD to prevent missed diagnoses.