Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: OAS1

Green List (high evidence)

Thomas Magg et al. identified four de novo heterozygous OAS1 gain-of-function variants in six patients with a polymorphic autoinflammatory immunodeficiency characterized by recurrent fever, dermatitis, inflammatory bowel disease, pulmonary alveolar proteinosis, and hypogammaglobulinemia.

Created: 22 Jun 2021, 11:02 a.m. | Last Modified: 22 Jun 2021, 11:02 a.m.

Panel Version: 2.434

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
recurrent fever; dermatitis; inflammatory bowel disease; pulmonary alveolar proteinosis; hypogammaglobulinemia.

Publications

• 34145065

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

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

Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.

Panel Version: 2.529

Additional publication identified by Boaz Palterer (PMID:34145065) supports the inclusion of this gene as Green on this panel. There are now at least 4 different gain-of-function heterozygous variants in the OAS1 gene identified in 8 unrelated families with 10 affected individuals (P5 in PMID:34145065 and C-II-1 in PMID:29455859 refer to the same individual).

Created: 29 Jun 2021, 11:12 a.m. | Last Modified: 29 Jun 2021, 11:12 a.m.

Panel Version: 2.437

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 2:41 p.m. | Last Modified: 20 Oct 2020, 2:41 p.m.

Panel Version: 2.337

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 34145065
• 29455859

Comment on list classification: Upgraded rating from Amber to Green following advice from Helen Brittain (Genomics England Clinical Team): There appear to be three unrelated families with variants and hypogammaglobulinaemia. I think this is a relevant phenotype for immune dysfunction.

Created: 18 May 2020, 8:26 a.m. | Last Modified: 18 May 2020, 8:26 a.m.

Panel Version: 2.169

Comment on list classification: Updated from Red to Amber, awaiting clinical review.

Created: 29 Apr 2020, 8:24 p.m. | Last Modified: 29 Apr 2020, 8:24 p.m.

Panel Version: 2.138

PMID:29455859 (Cho et al. 2018) performed WES in a family with Pulmonary alveolar proteinosis (PAP) with hypogammaglobulinemia. They identified a heterozygous missense variant in OAS1 in 3 affected siblings. The mother showed mosaicism, suggesting AD inheritance from the maternal side. The authors identify 2 additional OAS1 heterozygous de novo variants in 2 unrelated individuals with PAP + hypogammaglobulinemia.

Created: 29 Apr 2020, 8:23 p.m. | Last Modified: 29 Apr 2020, 8:23 p.m.

Panel Version: 2.137

Green List (high evidence)

Five individuals from three unrelated families including 3 sibs where the variant was present at mosaic level in one parent.

Created: 11 Apr 2020, 4:50 a.m. | Last Modified: 11 Apr 2020, 4:50 a.m.

Panel Version: 2.51

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinemia

Publications

• 29455859

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Added publication referenced by IUIS december 2019 update

Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.

Panel Version: 2.36

Publications

• 29455859