Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SEPT6

Green List (high evidence)

Gunderman et al. described stop loss variant in the X-linked SEPTIN6 gene, they identified 2 hemizygous male siblings. The researchers presented evidence characterized by severe congenital neutropenia, a profound lack of circulating B cells, and variable T cell lymphopenia, noting that maternal carriers show strong negative selection against the mutated allele in their hematopoietic cells. Clinical data and bone marrow analysis revealed progressive dysmyelopoiesis with myeloid tetraploidy and a predisposition to aneuploidy, while xenograft mouse models and spatial transcriptomics further demonstrated that the SEPTIN6 mutation leads to a significant reduction in early lymphoid progenitors rather than an absolute developmental block.

Renella et al. described a single patient with a de novo germline stop-loss mutation in the X-linked gene SEPT6 with a similar phenotype
Sources: Literature

Created: 6 May 2026, 8:20 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Congenital neutropenia; B cell deficiency; T cell lymphopenia; Abnormal newborn screening for SCID; Hypersegmented neutrophils; Myelodysplasia; Decreased circulating B cells; Leukopenia

Publications

• 42088107, 34677878