title: PRRT2-related disorders: further PKD and ICCA cases and review of the literature.
abstract: Recent studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). PRRT2 is a presynaptic protein which seems to play an important role in exocytosis and neurotransmitter release. PKD is the most common form of paroxysmal movement disorder characterized by recurrent brief involuntary hyperkinesias triggered by sudden movements. Here, we sequenced PRRT2 in 14 sporadic and 8 familial PKD and ICCA cases of Caucasian origin and identified three novel mutations (c.919C>T/p.Gln307, c.388delG/p.Ala130Profs 46, c.884G>A/p.Arg295Gln) predicting two truncated proteins and one probably damaging point mutation. A review of all published cases is also included. PRRT2 mutations occur more frequently in familial forms of PRRT2-related syndromes (80-100 %) than in sporadic cases (33-46 %) suggesting further heterogeneity in the latter. PRRT2 mutations were rarely described in other forms of paroxysmal dyskinesias deviating from classical PKD, as we report here in one ICCA family without kinesigenic triggers. Mutations are exclusively found in two exons of the PRRT2 gene at a high rate across all syndromes and with one major mutation (c.649dupC) in a mutational hotspot of nine cytosines, which is responsible for 57 % of all cases in all phenotypes. We therefore propose that genetic analysis rapidly performed in early stages of the disease is highly cost-effective and can help to avoid further unnecessary diagnostic and therapeutic interventions.
authors.affiliation: Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany. felicitas.becker@uni-tuebingen.de
authors.forename: Felicitas
authors.initials: F
authors.lastname: Becker
authors.forename: Julian
authors.initials: J
authors.lastname: Schubert
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Anttonen
authors.forename: Elina
authors.initials: E
authors.lastname: Liukkonen
authors.forename: Eija
authors.initials: E
authors.lastname: Gaily
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.forename: Stephan
authors.initials: S
authors.lastname: Müller
authors.forename: Nicole
authors.initials: N
authors.lastname: Heußinger
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellinghaus
authors.forename: Angela
authors.initials: A
authors.lastname: Robbiano
authors.forename: Anne
authors.initials: A
authors.lastname: Polvi
authors.forename: Simone
authors.initials: S
authors.lastname: Zittel
authors.forename: Tim J
authors.initials: TJ
authors.lastname: von Oertzen
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Tom
authors.initials: T
authors.lastname: Warner
authors.forename: Alexander
authors.initials: A
authors.lastname: Münchau
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D004421:Dystonia; D020936:Epilepsy, Benign Neonatal / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human