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de Sainte Agathe, J.M.* ; Pode-Shakked, B.* ; Naudion, S.* ; Michaud, V.* ; Arveiler, B.* ; Fergelot, P.* ; Delmas, J.* ; Keren, B.* ; Poirsier, C.* ; Alkuraya, F.S.* ; Tabarki, B.* ; Bend, E.* ; Davis, K.* ; Bebin, M.* ; Thompson, M.L.* ; Bryant, E.M.* ; Wagner, M. ; Hannibal, I.* ; Lenberg, J.* ; Krenn, M.* ; Wigby, K.M.* ; Friedman, J.R.* ; Iascone, M.* ; Cereda, A.* ; Miao, T.* ; Leguern, E.* ; Argilli, E.* ; Sherr, E.* ; Caluseriu, O.* ; Tidwell, T.* ; Bayrak-Toydemir, P.* ; Hagedorn, C.* ; Brugger, M.* ; Vill, K.* ; Morneau-Jacob, F.D.* ; Chung, W.* ; Weaver, K.N.* ; Owens, J.W.* ; Husami, A.* ; Chaudhari, B.P.* ; Stone, B.S.* ; Burns, K.* ; Li, R.* ; de Lange, I.M.* ; Biehler, M.* ; Ginglinger, E.* ; Gérard, B.* ; Stottmann, R.W.* ; Trimouille, A.*

ARF1-related disorder: Phenotypic and molecular spectrum.

J. Med. Genet. 60, 999-1005 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Epilepsy ; Human Genetics ; Sequence Analysis, Dna; Periventricular Heterotopia; Neuronal Migration; Mutations; Mechanism; Filamin; Genes
ISSN (print) / ISBN 0022-2593
e-ISSN 1468-6244
Zeitschrift Journal of Medical Genetics
Quellenangaben Band: 60, Heft: 10, Seiten: 999-1005 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)