Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia

Background: Agammaglobulinemia is a rare immune disorder characterized by deficient immunoglobulin production, primarily affecting the B cells of the immune system. Case Report: A 13-year-old girl was admitted to the hospital due to "recurrent respiratory infections for over 6 years, accompanied by cough and fever for more than 1 week". She had experienced recurrent fever, cough, and purulent sputum approximately once every 2 months. Investigation: Immunoglobulin testing revealed significantly decreased IgG and IgA levels, with both the ratio of B lymphocytes (CD3 ^- CD19 ⁺ )/ lymphocytes and the absolute B cell count being 0, leading to a preliminary diagnosis of immune deficiency. Genetic testing was performed on the patient, her younger brother and their parents to determine the specific type of immune deficiency. Results showed that the patient carried a heterozygous mutation in the SPI1 gene (c.566T>C, p.Ile189Thr), confirming a diagnosis of autosomal dominant agammaglobulinemia. This mutation was inherited from her mother; neither her father nor her younger brother carried it. A literature review indicated that the c.566T>C mutation in the SPI1 gene had not been previously reported. Additionally, we summarized the clinical and genetic characteristics of patients from different continents. The patient received anti-infection treatment with piperacillin-tazobactam and voriconazole, intravenous gamma globulin infusion, bronchoscopic lavage, and symptomatic treatment (e.g., antipyretic, antitussive, expectorant, and nutritional support). Her condition improved rapidly, and she was discharged. Long-term follow-up showed that she received monthly intravenous gamma globulin infusions at a local hospital. Conclusion: This study reports a case of autosomal dominant agammaglobulinemia caused by a novel SPI1 gene mutation. To date, this mutation has not been recorded in Chinese reference gene databases or the global Genome Aggregation Database (gnomAD). Our findings suggest that whole-exome sequencing for detecting such mutations could improve the identification and early diagnosis of agammaglobulinemia, particularly in homozygous individuals with SPI1 mutations. These SPI1 mutations may represent a novel therapeutic target for the agammaglobulinemia in the future.