title: Loss of Function of KCNC1 is associated with intellectual disability without seizures.
abstract: p.(Arg320His) mutation in the KCNC1 gene in human 11p15.1 has recently been identified in patients with progressive myoclonus epilepsies, a group of rare inherited disorders manifesting with action myoclonus, myoclonic epilepsy, and ataxia. This KCNC1 variant causes a dominant-negative effect. Here we describe three patients from the same family with intellectual disability and dysmorphic features. The three affected individuals carry a c.1015C>T (p.(Arg339*)) nonsense variant in KCNC1 gene. As previously observed in the mutant mouse carrying a disrupted KCNC1 gene, these findings reveal that individuals with a KCNC1 loss-of-function variant can present intellectual disability without seizure and epilepsy.
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.affiliation: Unité de Génétique Clinique, Maternité Port-Royal, HUPC, Hôpital Cochin, Paris, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Viot
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Lombardi
authors.affiliation: Unité de Génétique Clinique, Maternité Port-Royal, HUPC, Hôpital Cochin, Paris, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Jauny
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Billuart
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de Paris, Groupe Universitaire Paris Centre, Site Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D000328:Adult; D002648:Child; D018389:Codon, Nonsense; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D012640:Seizures / Q000175:diagnosis / Q000235:genetics*; D051670:Shaw Potassium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; C489597:KCNC1 protein, human; D051670:Shaw Potassium Channels