ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 17 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Sensory nerve-derived signaling coordinates oropharyngeal structural organization that supports suckling and vocalization in neonatal mice.Nature communications · 2026Article
- Investigating and correcting a rare pathogenic mutation in GDF11.HGG advances · 2026Article
- Gene-by-Environment Interactions Involving Maternal Exposures with Orofacial Cleft Risk in Filipinos.Genes · 2025Article
- gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling.Scientific reports · 2025Article
- Gdf11 regulates left-right asymmetry development through TGF-β signal.Cell proliferation · 2025Article
- Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Novel insights into the pleiotropic health effects of growth differentiation factor 11 gained from genome-wide association studies in population biobanks.BMC genomics · 2024Article
- Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans.Nature reviews. Genetics · 2024Review
- GDF11 and aging biology - controversies resolved and pending.The journal of cardiovascular aging · 2023Article
- GDF-11 as a Potential Cardiac Pro-Angiogenic Factor.JACC. Basic to translational science · 2023Article
- Functional substitutions of amino acids that differ between GDF11 and GDF8 impact skeletal development and skeletal muscle.Life science alliance · 2023Article
- MeCP2 regulateseLife · 2023Article
- De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement.American journal of human genetics · 2022Article
- ModelMatcher: A scientist-centric online platform to facilitate collaborations between stakeholders of rare and undiagnosed disease research.Human mutation · 2022Article
- Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures.American journal of human genetics · 2022Article
- Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases.Cell reports · 2022Article
- Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases.Experimental neurobiology · 2022Review
Corrections and comments
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Authors and funding
32 authors at 20 institutions in 4 countries.
Funding
Abstract
purposeGrowth 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.
methodsWe 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.
resultsPatients with variants in GDF11 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). gdf11 mutant zebrafish show craniofacial abnormalities and body segmentation defects that match 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 in our cohort are partial LOF variants.
conclusionGDF11 is needed for human development, particularly neuronal development, and LOF GDF11 alleles can affect the development of numerous organs and tissues.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.