Retinal disorders

Gene: POMGNT2

I don't know

The rating of this gene has been updated to Amber and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 2:08 p.m. | Last Modified: 30 Jan 2023, 2:08 p.m.

Panel Version: 3.26

Comment on classification: This gene should be rated AMBER as this gene has been associated with retinal phenotype in one patient and was supported by results from zebrafish models.

PMID:22958903 reported three unrelated families with Walker-Warburg syndrome caused by autosomal recessive inheritance. However, only one of these patients were presented with any retinal phenotypes (retinal dysplasia). Another patient had other ocular defects (microphthalmia and macrophthalmia). In addition, functional studies with zebrafish models showed that POMGNT2 knockdown replicated features of Walker-Warburg syndrome, which included underdeveloped eyes, where ventral fusion of the retina was delayed.

PMID:27066570 reported milder forms of muscular dystrophy associated with biallelic variants in POMGNT2 gene in three patients. However, retinal phenotypes were not reported in these patients.

This gene was associated with Walker-Warburg syndrome in both OMIM and G2P.

Created: 9 Jan 2023, 6:38 a.m. | Last Modified: 9 Jan 2023, 6:38 a.m.

Panel Version: 3.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, OMIM:614830

Publications

• 22958903
• 27066570

Review submitted on behalf of Robert Henderson, Mr Chien Wong, Mr CK Patel. Publications: Manzini, M. C., Tambunan, D. E., Hill, R. S., Yu, T. W., Maynard, T. M., Heinzen, E. L., Shianna, K. V., Stevens, C. R., Partlow, J. N., Barry, B. J., Rodriguez, J., Gupta, V. A., and 10 others.Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome.Am. J. Hum. Genet. 91: 541-547, 2012;

Created: 21 Dec 2022, 4:51 p.m. | Last Modified: 21 Dec 2022, 4:51 p.m.

Panel Version: 3.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscle Eye Brain disease, Walker Warburg disease; limb girdle muscular dystrophy