This report describes the syndrome vertebral hypersegmentation and orofacial anomalies (VHO); VHO exhibits autosomal dominant inheritance. A recent study has expanded the observed phenotypes associated with this disease. The gene implicated in VHO is GDF11, which encodes a ligand of TGF-beta receptors; it plays a role in specification of positional identity along the anterior/posterior axis during development. There is a single orthologous gene in Drosophila, myo, for which multiple genetic reagents have been generated including amorphic mutations, RNAi targeting constructs, and overexpression constructs. Dmel\myo is also orthologous to the human gene MSTN.
A UAS construct of the wild-type human Hsap\GDF11 gene has been introduced into flies, but has not been used in the context of this disease model.
Animals homozygous for an amorphic allele of Dmel\myo die during the pupal stage. Overexpression of a UAS construct with wild-type myo results in varying levels of lethality, dependent upon temperature and the GAL4 driver used. GAL4-driven overexpression has been used to characterize myo mutations analogous to variants implicated in VHO (see the 'Disease-Implicated Variants' table, below). The assay provides information on the severity of a characterized variant; a nonsense mutation was found to exhibit the most severe loss-of-function (no lethality observed in this assay).
[updated Oct. 2021 by FlyBase; FBrf0222196]
[VERTEBRAL HYPERSEGMENTATION AND OROFACIAL ANOMALIES; VHO](https://omim.org/entry/619122)
[GROWTH/DIFFERENTIATION FACTOR 11; GDF11](https://omim.org/entry/603936)
The original description of this disease was based on phenotypes observed in one family. Identification of additional patients with both de novo and inherited variants in GDF11 has expanded the range of phenotypes observed, including complex neurological, cardiovascular, connective tissue, ocular, and auditory phenotypes, in addition to the craniofacial and skeletal abnormalities originally described (Ravenscroft et al., 2021, pubmed:34113007, FBrf0251494).
Vertebral hypersegmentation and orofacial anomalies (VHO) is characterized by supernumerary cervical, thoracic, and/or lumbar vertebrae, in association with supernumerary ribs. Most patients also exhibit orofacial clefting and ear anomalies (Cox et al., 2019; pubmed:31215115). [from MIM:619122; 2021.10.15]
Vertebral hypersegmentation and orofacial anomalies (VHO) is caused by heterozygous mutation in the GDF11 gene. [from MIM:619122; 2021.10.15]
GDF11 encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The secreted signal acts globally to specify positional identity along the anterior/posterior axis during development. [Gene Cards, GDF11; 2021.10.15]
Many to one: multiple human genes to 1 Drosophila gene.
