Retinal disorders

Gene: GDF6

Comment on list classification: This gene has been promoted from Red to Amber. As there is not enough evidence to support a gene-disease association, this gene has been given an Amber rating.

Created: 22 Jan 2021, 11:43 a.m. | Last Modified: 22 Jan 2021, 11:43 a.m.

Panel Version: 2.124

PMID: 23307924 screened 279 patients with LCA and juvenile retinitis pigmentosa. One proband with compound heterozygous variants in GDF6 with diagnosed with LCA. Both parents of this proband were heterozygous for the variants.
Three other probands with heterozygous variants in GDF6 were also found; however, the probands unaffected parents were also heterozygous for these variants.
The authors also made mouse and zebrafish models and both models showed increased retinal apoptosis.

PMID: 32737436 looked at patients with CAKUT. Three families were found to have heterozygous variants in GDF6 (7 affected individuals). In all affected individuals there is a range of phenotypes (renal, skeletal, auricular and ocular anomalies). Ocular anomalies were not present in all individuals with the variants (2 of 7 individuals, both from different families). The ocular phenotypes that were seen in these patients were anisometropia with hyperopia, astigmatism, amblyopia, suspected micro-phthalmia, corneal opacities and short narrow palpebral fissures.

This gene is Green on the Structural eye disease panel (Version 1.42).

Created: 22 Jan 2021, 11:41 a.m. | Last Modified: 22 Jan 2021, 11:41 a.m.

Panel Version: 2.122

I don't know

The authors say: "In summary, we identified rare heterozygous GDF6 variants in 1.6% of all patients of our renal anomaly cohort, and in 5.4% of those patients additionally manifesting skeletal, ocular, or auricular abnormalities". The authors also cofirmed their findings in animal models.

Created: 6 Jan 2021, 8:48 a.m. | Last Modified: 6 Jan 2021, 8:48 a.m.

Panel Version: 2.38

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

Phenotypes
kidney hypodysplasia

Publications

• https://doi.org/10.1038/s41431-020-0678-9

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

Red List (low evidence)

LCA reported but variants are probably not rare enough

Created: 30 Aug 2019, 2:12 p.m. | Last Modified: 30 Aug 2019, 2:12 p.m.

Panel Version: 1.159