A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency.

Objectives: To describe the case of a young girl with severe congenital neutropenia caused by a homozygous variant in the Jagunal homolog 1 (JAGN1) gene, who later developed atypical diabetes.

Case presentation: JAGN1 deficiency disrupts neutrophil maturation, resulting in immunodeficiency and recurrent infections. Our patient also exhibited impaired humoral immunity, requiring immunoglobulin replacement therapy, which reduced infection frequency. Several years after the identification of her JAGN1 mutation, she developed atypical insulin-dependent diabetes mellitus - a condition not previously associated with JAGN1 mutations. This novel finding suggests a potential role for JAGN1 in pancreatic β-cell function.

Conclusions: This case expands the spectrum of JAGN 1-related immune dysfunction and introduces a potential link between JAGN1 deficiency and diabetes. We explore possible mechanisms underlying this association, highlighting the need for further research. Clinicians should consider JAGN1 mutations in the differential diagnosis of combined immune and metabolic disorders.