Corneal abnormalities (Version 1.13)

Description

Corneal abnormalities inclusion criteria
- Bilateral corneal signs
- Prior consultation with ophthalmologist who has a specialist interest in corneal dystrophies

Corneal abnormalities exclusion criteria
- Corneal opacity likely secondary to inflammatory disease or trauma (including surgical)
- Age-related corneal endothelial failure
- Keratoconus

Prior genetic testing guidance
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Corneal abnormalities prior genetic testing genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - TGFBI (BIGH3) gene screening in anterior corneal dystrophies (which accounts for approximately 80% of such families)

Closing statement
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

7 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Ellen Thomas (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Chris Campbell (NHS)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Chris Campbell (GEL)

Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other

43 Entities

43 reviewed, 32 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 43 Entitiess
Green Green List (high evidence)	ADAMTS18	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Microcornea, myopic chorioretinal atrophy, and telecanthus, 615458 Tags
Green Green List (high evidence)	ALDH18A1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes cutis laxa, corneal clouding, and mental retardation Cutis laxa, autosomal dominant 3 616603 Cutis laxa, autosomal recessive, type IIIA 219150 Tags
Green Green List (high evidence)	B3GLCT	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Peters-plus syndrome 261540 Tags
Green Green List (high evidence)	CHRDL1	2 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Megalocornea 1, X-linked 309300 X-linked megalocornea but can also cause lens subluxation or dislocation Tags
Green Green List (high evidence)	CHST6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Macular Corneal Dystrophy Macular corneal dystrophy 217800 Paediatric Macular corneal dystrophy (type 1 and type 2), AR Tags
Green Green List (high evidence)	COL8A2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Corneal dystrophy, Fuchs endothelial, 1, 136800 early onset fuchs endothelial corneal dystrophy Tags
Green Green List (high evidence)	DCN	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Corneal dystrophy, congenital stromal 610048 Tags
Green Green List (high evidence)	GJA1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Oculodentodigital dysplasia, OMIM:164200 Oculodentodigital dysplasia, autosomal recessive, OMIM:257850 Tags
Green Green List (high evidence)	GSN	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green Phenotypes Amyloidosis, Finnish type, OMIM:105120 Tags
Green Green List (high evidence)	HMX1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Oculoauricular syndrome 612109 Tags
Green Green List (high evidence)	KERA	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Cornea plana 2, autosomal recessive 217300 Tags
Green Green List (high evidence)	KRT12	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Meesmann corneal dystrophy, 122100 Tags
Green Green List (high evidence)	KRT3	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Meesmann corneal dystrophy, 122100 Tags
Green Green List (high evidence)	LTBP2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma 251750 Tags
Green Green List (high evidence)	MAF	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Cataract, pulverulent or cerulean, with or without microcornea, 610202 Cataract 21, multiple types 610202 Tags
Green Green List (high evidence)	MIR184	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes ENDOTHELIAL DYSTROPHY, IRIS HYPOPLASIA, CONGENITAL CATARACT, AND STROMAL THINNING SYNDROME EDICT syndrome 614303 Keratoconus Tags locus-type-rna-micro
Green Green List (high evidence)	OVOL2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Corneal dystrophy, posterior polymorphous, 1 122000 Tags promoter
Green Green List (high evidence)	PIK3R1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes SHORT syndrome 269880 Tags
Green Green List (high evidence)	PIKFYVE	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Corneal fleck dystrophy 121850 Corneal fleck dystrophy, AD, paediatric Tags
Green Green List (high evidence)	PITX2	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Anterior segment dysgenesis 4 137600 AD Axenfeld-Rieger syndrome, type 1 180500 AD Ring dermoid of cornea 180550 Tags
Green Green List (high evidence)	PRDM5	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Brittle Cornea Syndrome Brittle cornea syndrome 2, 614170 Tags
Green Green List (high evidence)	RAB18	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Warburg micro syndrome 3 614222 Tags
Green Green List (high evidence)	RAB3GAP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Warburg micro syndrome 1 600118 Tags
Green Green List (high evidence)	RAB3GAP2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Phenotypes Martsolf syndrome 1, OMIM:212720 Warburg micro syndrome 2, OMIM:614225 Tags
Green Green List (high evidence)	SLC16A12	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Cataract, juvenile, with microcornea and glucosuria, 612018 Tags
Green Green List (high evidence)	SLC4A11	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Corneal Dystrophy, Recessive Corneal endothelial dystrophy 2, autosomal recessive, 217700 Congenital Hereditary Endothelial Dystrophy Tags
Green Green List (high evidence)	TACSTD2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Corneal Dystrophy, Dominant/Recessive Corneal dystrophy, gelatinous drop-like, 204870 Tags
Green Green List (high evidence)	TGFBI	3 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Corneal dystrophy, Avellino type 607541 Corneal dystrophy, epithelial basement membrane 121820 Corneal dystrophy, Groenouw type I 121900 Corneal dystrophy, lattice type I 122200 Corneal dystrophy, lattice type IIIA 608471 Corneal dystrophy, Reis-Bucklers type 608470 Corneal dystrophy, Thiel-Behnke type 602082 Tags
Green Green List (high evidence)	UBIAD1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Schnyder Crystalline Corneal Dystrophy Corneal dystrophy, Schnyder type 121800 Schnyder corneal dystrophy , AD, early onset Tags
Green Green List (high evidence)	VSX1	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Keratoconus 1 148300 Tags
Green Green List (high evidence)	ZEB1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GDL Corneal Abnormalities panel Radboud University Medical Center, Nijmegen Phenotypes Corneal dystrophy, posterior polymorphous, 3, 609141 Posterior polymorphous corneal dystrophy 3 (PPCD3), AD Fuchs endothelial corneal dystrophy Tags
Green Green List (high evidence)	ZNF469	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GDL Corneal Abnormalities panel Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Brittle cornea syndrome, 229200 Tags
Amber Amber List (moderate evidence)	AGBL1	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes Corneal dystrophy, Fuchs endothelial, 8, 615523 (3) Tags
Red Red List (low evidence)	ABCA3	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red GDL Corneal Abnormalities panel Phenotypes Cataract-microcornea syndrome Tags
Red Red List (low evidence)	APOA1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Corneal clouding, autosomal recessive Familial LCAT deficiency Tags
Red Red List (low evidence)	BEST1	2 reviews	Not set	Sources Emory Genetics Laboratory Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Best Vitelliform Macular Dystrophy (BVMD), Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC), Additional features include congenital or early-onset cataracts, microcornea, hypermetrophic, and shallow anterior chamber, Autosomal Recessive Bestrophinopathy (ARB) Best macular dystrophy, 153700 Tags
Red Red List (low evidence)	CYP4V2	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Phenotypes Bietti crystalline corneoretinal dystrophy 210370 Tags
Red Red List (low evidence)	GJA8	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Phenotypes Cataract-Microcornea Syndrome Tags
Red Red List (low evidence)	GLS	2 reviews 2 red	Unknown	Sources Expert Review Red GDL Corneal Abnormalities panel Phenotypes Corneal dystrophy abstract Tags watchlist
Red Red List (low evidence)	LAMB2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red GDL Corneal Abnormalities panel Phenotypes Pierson syndrome 609049 Tags
Red Red List (low evidence)	MED25	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red GDL Corneal Abnormalities panel Phenotypes Basel-Vanagait-Smirin-Yosef syndrome 616449 Tags founder-effect
Red Red List (low evidence)	PAX6	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes ?Morning glory disc anomaly 120430 Aniridia 106210 Cataract with late-onset corneal dystrohpy 106210 Coloboma of optic nerve 120430 Coloboma ocular 120200 Foveal hypoplasia 1 136520 Gillespie syndrome 206700 Keratitis 148190 Optic nerve hypoplasia 165550 Peters anomaly 604229 Anterior segment dysgenesis 5, multiple subtypes 604229 Tags
Red Red List (low evidence)	PDGFRB	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Tags

Major version comments

09/03/2017 Revised and approved to Version 1.0 after expert and internal review.

Corneal abnormalities (Version 1.13)

7 reviewers

43 Entities

43 reviewed, 32 green

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