RT Journal Article SR Electronic T1 ARF1 haploinsufficiency causes periventricular nodular heterotopia with variable clinical expressivity JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 781 OP 784 DO 10.1136/jmedgenet-2021-107783 VO 59 IS 8 A1 Simone Gana A1 Antonella Casella A1 Sara Cociglio A1 Elena Tartara A1 Elisa Rognone A1 Elisa Giorgio A1 Anna Pichiecchio A1 Simona Orcesi A1 Enza Maria Valente YR 2022 UL http://jmg.bmj.com/content/59/8/781.abstract AB 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.