ArticleEuropean journal of human genetics : EJHG2019
A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS/ERK1/2 pathway.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Growth factor analysis in children with non-syndromic orofacial clefts: a systematic review.BMC oral health · 2026Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Evidence-based classification of genes implicated in craniosynostosis disorders using the ClinGen curation framework.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Malformation Pattern and Molecular Findings in theMedical sciences (Basel, Switzerland) · 2025Review
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study.Birth defects research · 2025Article
- Biological pathways leading to septo-optic dysplasia: a review.Orphanet journal of rare diseases · 2025Review
- Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.Children (Basel, Switzerland) · 2023Review
- FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner.Disease models & mechanisms · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation ofJournal of the Endocrine Society · 2020Article
- MicroRNA-761 targets FGFR1 to suppress the malignancy of osteosarcoma by deactivating PI3K/Akt pathway.OncoTargets and therapy · 2019Article
- Solitary Median Maxillary Central Incisor in Hartsfield Syndrome: A Case Report.International journal of clinical pediatric dentistryArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hartsfield syndrome (HS) is an ultrarare developmental disorder mainly featuring holoprosencephaly and ectrodactyly. It is caused by heterozygous or biallelic variants in FGFR1. Recently, a dominant-negative effect was suggested for FGFR1 variants associated with HS. Here, exome sequencing analysis in a 12-year-old boy with HS disclosed a novel de novo heterozygous variant c.1934C>T in FGFR1 predicted to cause the p.(Ala645Val) amino-acid substitution. In order to evaluate whether the variant, changing a highly conserved residue of the kinase domain, affects FGFR1 function, biochemical studies were employed. We measured the FGFR1 receptor activity in FGF2-treated cell lines exogenously expressing wild-type or Ala645Val FGFR1 by monitoring the activation status of FGF2/FGFR1 downstream pathways. Our analysis highlighted that RAS/ERK1/2 signaling was significantly perturbed in cells expressing mutated FGFR1, in comparison with control cells. We also provided preliminary evidence showing a modulation of the autophagic process in cells expressing mutated FGFR1. This study expands the FGFR1 mutational spectrum associated with HS, provides functional evidence further supporting a dominant-negative effect of this category of FGFR1 variants and offers initial insights on dysregulation of autophagy in HS.
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