Glaucoma (developmental)
Gene: DDX58Added new-gene-name tag, new approved HGNC gene symbol for DDX58 is RIGI.Created: 21 Nov 2022, 3:21 p.m. | Last Modified: 21 Nov 2022, 3:21 p.m.
Panel Version: 1.42
Comment on list classification: At least 4 gain-of-function variants identified in 5 unrelated families with Singleton-Merten syndrome 2, including glaucoma in all affected individuals (PMIDs: 25620203; 30574673; 33495304). Therefore, this now reaches threshold for a rating upgrade from Amber to Green.Created: 5 Feb 2021, 11:10 a.m. | Last Modified: 5 Feb 2021, 11:10 a.m.
Panel Version: 1.11
DDX58 is associated with Singleton-Merten syndrome in OMIM and Gene2Phenotype.
- 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, 10:58 a.m. | Last Modified: 5 Feb 2021, 10:58 a.m.
Panel Version: 1.10
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Singleton-Merten syndrome 2, OMIM:616298; Singleton-Merten syndrome 2, MONDO:0014575
Publications
Yang, two families with childhood onset glaucoma; Ferreira one family with childhood onset glaucomaCreated: 19 Jun 2019, 3:32 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities.
Publications
Promoted from amber to green as there is sufficient evidence.Created: 24 Apr 2019, 2:38 p.m.
Submitted on behalf of Professor Nicola Ragge (Wessex and West Midlands GLH). Yang, two families with childhood onset glaucoma; Ferreira one family with childhood onset glaucomaCreated: 17 Apr 2019, 3:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities.
Publications
Comment on list classification: Feedback from Arianna Tucci: keep as amber for now.Created: 26 Apr 2017, 8:35 a.m.
Comment on list classification: Does not seem to be enough evidence yet for this gene to be green; keep as amber?Created: 12 Apr 2017, 2:37 p.m.
Comment on list classification: Two families described in PMID:25620203 with Singleton-Merten syndrome 2 who displayed glaucoma. Only this publication was found in literature search. Possible gene in Gene2Phenotype.Created: 12 Apr 2017, 2:36 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities.
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag new-gene-name tag was added to gene: DDX58.
Publications for gene: DDX58 were set to 2509; 3588; 25620203
Gene: ddx58 has been classified as Green List (High Evidence).
Phenotypes for gene: DDX58 were changed from Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities. to Singleton-Merten syndrome 2, OMIM:616298; Singleton-Merten syndrome 2, MONDO:0014575
27/04/2017: Revised after review and further curation, with clinical input, and promoted to version 1.
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for DDX58 were set to 2509; 3588;25620203
This gene has been classified as Amber List (Moderate Evidence).
DDX58 was created by Chricampbell
DDX58 was added to Glaucoma (developmental)panel. Sources: GDL Glaucoma panel