TY - JOUR T1 - <em>ARF1</em> haploinsufficiency causes periventricular nodular heterotopia with variable clinical expressivity JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2021-107783 SP - jmedgenet-2021-107783 AU - Simone Gana AU - Antonella Casella AU - Sara Cociglio AU - Elena Tartara AU - Elisa Rognone AU - Elisa Giorgio AU - Anna Pichiecchio AU - Simona Orcesi AU - Enza Maria Valente Y1 - 2021/08/05 UR - http://jmg.bmj.com/content/early/2021/08/04/jmedgenet-2021-107783.abstract N2 - 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. ER -