Congenital nystagmus
Gene: GDF6
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
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
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
Gene: gdf6 has been classified as Red List (Low Evidence).
Phenotypes for gene: GDF6 were changed from to Leber congenital amaurosis 17, MIM# 615360
Publications for gene: GDF6 were set to
Mode of inheritance for gene: GDF6 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: gdf6 has been classified as Red List (Low Evidence).
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