Clefting disorders

Gene: GDF11

I don't know

Amber rating in view of the supportive animal model.

Created: 1 Feb 2021, 7:45 a.m. | Last Modified: 1 Feb 2021, 7:45 a.m.

Panel Version: 0.48

Green List (high evidence)

Ravenscroft et al. (2021) report 6 probands who presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). They found de novo and inherited variants in GDF11. gdf11 mutant zebrafish showed craniofacial abnormalities and body segmentation defects that matched some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants are partial LOF variants.

Created: 7 Oct 2021, 12:12 a.m. | Last Modified: 7 Oct 2021, 12:12 a.m.

Panel Version: 0.142

In 5 affected members over 3 generations of a family segregating vertebral hypersegmentation and orofacial anomalies, Cox et al. (2019) identified heterozygosity for a missense mutation in the GDF11 gene (R298Q) that was not found in unaffected family members or in public variant databases. Functional analysis demonstrated that the R298Q substitution prevents cleavage to the active form of the protein, resulting in loss of function.
Sources: Expert list

Created: 1 Feb 2021, 1:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Vertebral hypersegmentation and orofacial anomalies (VHO), OMIM #619122

Publications

• PubMed: 31215115, 34113007