ARF1 haploinsufficiency causes periventricular nodular heterotopia with variable clinical expressivity

Simone Gana, Antonella Casella, Sara Cociglio, Elena Tartara, Elisa Rognone, Elisa Giorgio, Anna Pichiecchio, Simona Orcesi, Enza Maria Valente

Research output: Contribution to journalArticlepeer-review


The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1 in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.

Original languageEnglish
JournalJournal of Medical Genetics
Publication statusE-pub ahead of print - Aug 5 2021


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