Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11.

ABSTRACT:

Purpose

Growth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with a dominant human disease in a family with variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum associated with GDF11 variants and document the nature of the variants.

Methods

We present a cohort of six probands with de novo and inherited nonsense/frameshift (4/6 patients) and missense (2/6) variants in GDF11. We generated gdf11 mutant zebrafish to model loss of gdf11 phenotypes and used an overexpression screen in Drosophila to test variant functionality.

Results

Patients with variants in GDF11 presented with craniofacial (5/6), verteb

SUBMITTER: Ravenscroft TA 

PROVIDER: S-EPMC8487929 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature