Glaucoma congenital

Gene: DDX58

Green List (high evidence)

DDX58 is associated with Singleton-Merten syndrome in OMIM and Gene2Phenotype.

At least 4 gain-of-function variants identified in 5 unrelated families with Singleton-Merten syndrome 2, including glaucoma in all affected individuals:

- Jang et al. 2015 (PMID: 25620203) - 2 unrelated Korean families with glaucoma and skeletal abnormalities, and different heterozygous variants in DDX58 (c.1118A>C and c.803G>T, respectively). One family additionally exhibited aortic calcification, and both families had normal dentition. Functional studies showed that both variants confer constitutive activation, resulting in increased interferon activity and interferon-stimulated gene expression.

- Ferreira et al. 2019 (PMID: 30574673) - 2 individuals from one family with SMS, including glaucoma, aortic and valvular calcification, tendon rupture, psoriasiform skin rash, and dental abnormalities. A heterozygous DDX58 gain-of-function variant (c.1551G>C) was identified by WES which resulted in constitutive upregulation of type I interferon.

- Prasov et al. 2021 (PMID: 33495304) - A heterozygous DDX58 variant (c.1529A>T) was identified in 5 individuals from 2 unrelated families from different ethnic backgrounds. Phenotypes varied with some being severely affected by systemic features and others solely with glaucoma. However, all affected subjects presented juvenile open-angle glaucoma. Functional analysis demonstrated the variant confers a dominant gain-of-function effect on interferon activity.

Created: 5 Feb 2021, 11:19 a.m. | Last Modified: 5 Feb 2021, 11:19 a.m.

Panel Version: 1.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Singleton-Merten syndrome 2, OMIM:616298

Publications

• 25620203
• 30574673
• 33495304

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

I don't know

At least two families reported where glaucoma was a feature of the presenting phenotype.
Sources: Expert list

Created: 2 Aug 2020, 10:18 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Singleton-Merten syndrome 2, MIM# 616298

Publications

• 25620203