Skeletal dysplasia

Gene: GDF6

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

• 30733656
• 29130651
• 26643732
• 19129173
• 23307924
• 32737436

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

Red List (low evidence)

Please note the variants originally reported in association with Klippel-Feil syndrome are present at high frequencies in gnomad (50-200 hets).

Created: 7 Dec 2020, 6:21 a.m. | Last Modified: 7 Dec 2020, 6:21 a.m.

Panel Version: 0.5567

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Klippel-Feil syndrome 1, autosomal dominant 118100

Publications

• 18425797
• 19129173

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

• PMID: 32737436