Intellectual disability syndromic and non-syndromic
Gene: SAMD9

SAMD9 (sterile alpha motif domain containing 9)
EnsemblGeneIds (GRCh38): ENSG00000205413
EnsemblGeneIds (GRCh37): ENSG00000205413
OMIM: 610456, Gene2Phenotype
SAMD9 is in 12 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Variable neurodevelopmental phenotype as noted.
Created: 23 May 2024, 5:47 a.m. | Last Modified: 23 May 2024, 5:47 a.m.

Panel Version: 0.5898

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
MIRAGE Syndrome, MIM#617053

Created: 23 May 2024, 5:47 a.m.
Last Modified: 23 May 2024, 5:47 a.m.
Panel version: 0.5898

Raluca Rusu (Other)

Red List (low evidence)

Variants in SAMD9 have been reported in the literature in association with MIRAGE syndrome through a gain of function mechanism. Reported phenotypes in these patients include myelodysplasia, recurrent infections, restricted growth, adrenal hypoplasia and genital phenotypes. At least seven different studies reported eight different individuals with molecularly confirmed SAMD9 variants who also presented with a neurodevelopmental phenotype presenting with developmental delay and variable cognitive impairment with severe language delay in addition to the typical MIRAGE syndrome phenotype.
https://doi.org/10.1016/j.dscb.2022.100045- additional paper describing three siblings with MIRAGE syndrome and variable degrees of cognitive impairment.
Reported life span in most MIRAGE syndrome patients is below 3 years, hence cognitive function might not be properly assessed in majority of these patients.

Refuting evidence:
PMID: 31572304- inherited SAMD9 variant described- proband presented with typical MIRAGE phenotype early in infancy after which phenotype improved with no cognitive impairment reported at 14 years of age. Variant inherited from her phenotypically unaffected mother. Both mother and daughter had an additional somatically acquired revertant nonsense variant found in cis. Revertant variant would have only occurred in the haematopoietic linage which does not explain the lack of phenotypes affecting other systems such as lack of cognitive impairment in this patient and her mother.
Created: 22 May 2024, 10:12 a.m. | Last Modified: 22 May 2024, 10:12 a.m.

Panel Version: 0.5881

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
MIRAGE Syndrome, MIM#617053

Publications

Mode of pathogenicity
Other

Created: 22 May 2024, 10:12 a.m.
Last Modified: 22 May 2024, 10:12 a.m.
Panel version: 0.5881

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

MIRAGE Syndrome, MIM#617053

OMIM

610456

Clinvar variants

Variants in SAMD9

Penetrance

None

Publications

Panels with this gene