Congenital nystagmus

Gene: GDF6

Red List (low evidence)

GDF6 (growth differentiation factor 6)
EnsemblGeneIds (GRCh38): ENSG00000156466
EnsemblGeneIds (GRCh37): ENSG00000156466
OMIM: 601147, Gene2Phenotype
GDF6 is in 7 panels

3 reviews

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

Only the association with Multiple synostoses syndrome 4 (MIM#617898) is convincing with 3 large families with multiple affecteds and variants being absent in gnomAD.


Reports for Klippel-Feil syndrome 1 (MIM#MIM#118100); Leber congenital amaurosis 17(MIM# 615360) and Microphthalmia, isolated 4 (MIM#613094) and renal abnormalities are tenuous.
The papers sequenced only GDF6 and the variants are present in gnomAD at very high counts for an AD condition (50-350 hets).
The AR association for LCA is also tenuous as only 1 compound het was reported and 3 hets were hypothesised to be missing a 2nd hit.
Created: 6 Dec 2021, 3:30 a.m. | Last Modified: 6 Dec 2021, 3:30 a.m.
Panel Version: 0.10101

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Klippel-Feil syndrome 1, autosomal dominantMIM#118100; Leber congenital amaurosis 17 (MIM#615360); Microphthalmia, isolated 4 (MIM#613094); Multiple synostoses syndrome 4 (MIM#617898)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

PMID: 23307924 screened 279 patients with LCA and juvenile retinitis pigmentosa. One proband with compound heterozygous missense variants in GDF6 with diagnosed with LCA. Both parents of this proband were heterozygous for the variants.
Three other probands with heterozygous missense 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.

Note variants in this gene are associated with a variety of other phenotypes, including microphthalmia.
Created: 25 Oct 2021, 2:23 a.m. | Last Modified: 25 Oct 2021, 2:23 a.m.
Panel Version: 0.31

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Leber congenital amaurosis 17, MIM# 615360

Publications

Belinda Chong (Victorian Clinical Genetics Services)

Green List (high evidence)

Three individuals (three families) with kidney hypodysplasia and extrarenal manifestations, two of them additionally manifesting skeletal, ocular, or auricular abnormalities.

Two with same variant c.746C>A p.(Ala249Glu) and the third with c.112G>C p.(Gly38Arg).

"CRISPR/Cas9-derived knockout of Gdf6 attenuated migration of murine IMCD3 cells, an effect rescued by expression of wild-type but not mutant GDF6, indicating affected variant function regarding a fundamental developmental process. Knockdown of gdf6 in Xenopus laevis resulted in impaired pronephros development."
Created: 7 Dec 2020, 6:02 a.m. | Last Modified: 7 Dec 2020, 6:02 a.m.
Panel Version: 0.5567

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

Phenotypes
Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Expert list
Phenotypes
  • Leber congenital amaurosis 17, MIM# 615360
OMIM
601147
Clinvar variants
Variants in GDF6
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: gdf6 has been classified as Red List (Low Evidence).

25 Oct 2021, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: GDF6 were changed from to Leber congenital amaurosis 17, MIM# 615360

25 Oct 2021, Gel status: 1

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: GDF6 were set to

25 Oct 2021, Gel status: 1

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: GDF6 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

25 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: gdf6 has been classified as Red List (Low Evidence).

6 Oct 2021, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: GDF6 was added gene: GDF6 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list Mode of inheritance for gene: GDF6 was set to