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

We aimed to report the clinical and immunological characteristics of variant type X91⁺ chronic granulomatous disease (CGD) in a Chinese cohort.

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.

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 X91⁰ 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.

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.