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Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 SEPT6 Ida Ertmanska Tag watchlist tag was added to gene: SEPT6.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 SEPT6 Ida Ertmanska Phenotypes for gene: SEPT6 were changed from Congenital neutropenia; B cell deficiency; T cell lymphopenia; Abnormal newborn screening for SCID; Hypersegmented neutrophils; Myelodysplasia; Decreased circulating B cells; Leukopenia to severe congenital neutropenia, MONDO:0018542; Immunodeficiency, HP:0002721; Congenital neutropenia; B cell deficiency; T cell lymphopenia; Abnormal newborn screening for SCID; Hypersegmented neutrophils; Myelodysplasia; Decreased circulating B cells; Leukopenia
Primary immunodeficiency or monogenic inflammatory bowel disease v9.28 SEPT6 Ida Ertmanska Classified gene: SEPT6 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v9.28 SEPT6 Ida Ertmanska Added comment: Comment on list classification: To date, there are 2 unrelated male individuals reported in literature with hemizygous variants in SEPT6 and severe congenital neutropenia. Hence, this gene should remain Amber with the current evidence. A 'watchlist' tag was added in anticipation of more case reports.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.28 SEPT6 Ida Ertmanska Gene: sept6 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.27 SEPT6 Ida Ertmanska edited their review of gene: SEPT6: Added comment: PMID: 42088107 Gunderman et al., 2026
2 male sibs with severe nonsyndromic congenital neutropenia, absent circulating B cells, marrow mature myeloid, and rare plasma cell accumulation, as well as tetraploidy, with disease reversal following myeloablative HSCT. Older sibling had T-cell receptor excision circles (TRECs) of 9 copies (normal >20), while younger brother had 0 copies. No infectious symptoms were present. WGS detected a hemizygous SEPTIN6 (NM_145799.4) c.1282T>A; p.*428Kext*9 variant in both brothers (het in the unaffected mother) - diagnosed with X-linked SEPTIN6-related immunodeficiency.

PMID: 34677878 Renella et al., 2023
Report of a Caucasian male proband, presented with severe neutropenia associated with dysmyelopoiesis and tetraploidy as a newborn. The absolute neutrophil count (ANC) was 0.5 G/L at birth, subsequently 0-0.2 G/L. At age 1 year he underwent an allogeneic HLA-DQ-mismatched unrelated HSCT. WGS detected a hemizygous c.1282T>C, p.*428Glnext*9 variant in SEPT6. Second somatic SEPT6 variant was detected in cis: c.43C>T, p.Arg15* (14% of reads).

This gene is not yet associated with a disease entity in OMIM, ClinGen, or G2P (accessed 29th July 2026).; Changed rating: AMBER; Changed publications to: 42088107, 34677878; Changed phenotypes to: severe congenital neutropenia, MONDO:0018542, Immunodeficiency, HP:0002721; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v9.27 SEPT6 Ida Ertmanska commented on gene: SEPT6
Primary immunodeficiency or monogenic inflammatory bowel disease v9.27 SEPT6 Ida Ertmanska Tag new-gene-name tag was added to gene: SEPT6.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.1 SEPT6 Boaz Palterer gene: SEPT6 was added
gene: SEPT6 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SEPT6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SEPT6 were set to 42088107, 34677878
Phenotypes for gene: SEPT6 were set to Congenital neutropenia; B cell deficiency; T cell lymphopenia; Abnormal newborn screening for SCID; Hypersegmented neutrophils; Myelodysplasia; Decreased circulating B cells; Leukopenia
Penetrance for gene: SEPT6 were set to unknown
Review for gene: SEPT6 was set to GREEN
Added comment: 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