<i>ARF1</i>-related disorder: phenotypic and molecular spectrum - Sorbonne Université Access content directly
Journal Articles Journal of Medical Genetics Year : 2023

ARF1-related disorder: phenotypic and molecular spectrum

Ben Pode-Shakked
Sophie Naudion
  • Function : Author
Vincent Michaud
Benoit Arveiler
  • Function : Author
Patricia Fergelot
  • Function : Author
Jean Delmas
Boris Keren
  • Function : Author
Céline Poirsier
  • Function : Author
Fowzan S Alkuraya
Brahim Tabarki
  • Function : Author
Eric Bend
Kellie Davis
  • Function : Author
Martina Bebin
Michelle L Thompson
Emily M Bryant
Matias Wagner
Iris Hannibal
  • Function : Author
Jerica Lenberg
  • Function : Author
Martin Krenn
Kristen M Wigby
  • Function : Author
Jennifer R Friedman
  • Function : Author
Maria Iascone
Anna Cereda
Térence Miao
  • Function : Author
Eric Leguern
Emanuela Argilli
  • Function : Author
Elliott Sherr
  • Function : Author
Oana Caluseriu
  • Function : Author
Timothy Tidwell
  • Function : Author
Pinar Bayrak-Toydemir
  • Function : Author
Caroline Hagedorn
  • Function : Author
Melanie Brugger
Katharina Vill
  • Function : Author
Wendy Chung
Kathryn N Weaver
Joshua W Owens
  • Function : Author
Ammar Husami
Bimal P Chaudhari
  • Function : Author
Brandon S Stone
  • Function : Author
Katie Burns
  • Function : Author
Rachel Li
  • Function : Author
Iris M de Lange
  • Function : Author
Margaux Biehler
  • Function : Author
Emmanuelle Ginglinger
  • Function : Author
Bénédicte Gérard
  • Function : Author
Rolf W Stottmann
  • Function : Author
Aurélien Trimouille


Purpose ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. Methods We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. Results De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. Conclusion We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.


Human genetics
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Origin : Publication funded by an institution
Licence : CC BY NC - Attribution - NonCommercial

Dates and versions

hal-04191246 , version 1 (30-08-2023)



Jean-Madeleine de Sainte Agathe, Ben Pode-Shakked, Sophie Naudion, Vincent Michaud, Benoit Arveiler, et al.. ARF1-related disorder: phenotypic and molecular spectrum. Journal of Medical Genetics, 2023, ⟨10.1136/jmg-2022-108803⟩. ⟨hal-04191246⟩
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