Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SAMD9

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 12:01 p.m. | Last Modified: 24 Feb 2025, 12:01 p.m.

Panel Version: 7.26

Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the association of SAMD9 gene with immunodeficiency and auto-inflammation. Hence, this gene should be promoted to green rating in the next GMS update.

Created: 17 Sep 2024, 11:34 a.m. | Last Modified: 17 Sep 2024, 11:34 a.m.

Panel Version: 6.8

PMID:27182967 reported 11 patients from 10 unrelated families with a syndromic adrenal hypoplasia, which was named as MIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, MIM #617053). These patients were identified with eight different monoallelic variants in SAMD9 gene and 10 patients were reported with recurrent invasive infections.

PMID:31620126 reported a patient presenting with prominent gastrointestinal tract involvement and immunodeficiency, but without any sign of adrenal insufficiency typical for MIRAGE syndrome. This patient was identified with a novel SAMD9 variant (p.Arg824Gln).

PMID:33423168 presented the evidence of immunodeficiency and auto-inflammation in 10 patients genetically diagnosed with MIRAGE syndrome.

This gene has been associated with relevant phenotypes in both OMIM (MIM #617053) and Gene2Phenotype ('definitive' rating on the DD panel).

Created: 17 Sep 2024, 11:30 a.m. | Last Modified: 17 Sep 2024, 11:30 a.m.

Panel Version: 6.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
MIRAGE syndrome, OMIM:617053

Publications

• 27182967
• 31620126
• 33423168

Evidence in literature of immunodeficiency in several individuals with SAMD9-related MIRAGE syndrome. (PMID: 31620126, 31620126, 28202457, 33423168).

Created: 30 Aug 2024, 9:51 a.m. | Last Modified: 30 Aug 2024, 9:51 a.m.

Panel Version: 6.4

Phenotypes
Immunodeficiency; Recurrent infections; Mild decrease in natural killer cell activity; Low CD4-to-CD8 ratio; Mild decrease in neutrophil phagocytic activity

Publications

• PMID: 31620126
• 31620126
• 28202457
• 33423168

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): SAMD9 .PanelApp HGNC gene symbol check: SAMD9 . IUIS Disease: SAMD9 . IUIS Inheritance: AD (GOF) .T cells: N/A, .B cells: Not reported, .IUIS Other affected cells: N/A. IUIS Associated features: IUGR with gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DyskeratosIs Congenita (DKC), Myelodysplasia, Short Telomeres

Created: 6 Jul 2018, 10:37 a.m.

I don't know

Complex genetics - germline gain-of-function may be superseded by somatic inactivation (including by monosomy 7), resulting in myelodysplasia/AML

Created: 29 Jun 2018, 4:41 p.m.

Mode of inheritance
Other

Phenotypes
MIRAGE syndrome (Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy); ataxia-thrombocytopenia syndrome

Publications

• 28487541
• 29175836
• 29266745
• 29535429