title: Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.
abstract: Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.
authors: Department of Neurology, UCSF, San Francisco, CA 94158, USA.
authors: Hsien-Yang
authors: HY
authors: Lee
authors: Yong
authors: Y
authors: Huang
authors: Nadine
authors: N
authors: Bruneau
authors: Patrice
authors: P
authors: Roll
authors: Elisha D O
authors: ED
authors: Roberson
authors: Mark
authors: M
authors: Hermann
authors: Emily
authors: E
authors: Quinn
authors: James
authors: J
authors: Maas
authors: Robert
authors: R
authors: Edwards
authors: Tetsuo
authors: T
authors: Ashizawa
authors: Betul
authors: B
authors: Baykan
authors: Kailash
authors: K
authors: Bhatia
authors: Susan
authors: S
authors: Bressman
authors: Michiko K
authors: MK
authors: Bruno
authors: Ewout R
authors: ER
authors: Brunt
authors: Roberto
authors: R
authors: Caraballo
authors: Bernard
authors: B
authors: Echenne
authors: Natalio
authors: N
authors: Fejerman
authors: Steve
authors: S
authors: Frucht
authors: Christina A
authors: CA
authors: Gurnett
authors: Edouard
authors: E
authors: Hirsch
authors: Henry
authors: H
authors: Houlden
authors: Joseph
authors: J
authors: Jankovic
authors: Wei-Ling
authors: WL
authors: Lee
authors: David R
authors: DR
authors: Lynch
authors: Shehla
authors: S
authors: Mohammed
authors: Ulrich
authors: U
authors: Müller
authors: Mark P
authors: MP
authors: Nespeca
authors: David
authors: D
authors: Renner
authors: Jacques
authors: J
authors: Rochette
authors: Gabrielle
authors: G
authors: Rudolf
authors: Shinji
authors: S
authors: Saiki
authors: Bing-Wen
authors: BW
authors: Soong
authors: Kathryn J
authors: KJ
authors: Swoboda
authors: Sam
authors: S
authors: Tucker
authors: Nicholas
authors: N
authors: Wood
authors: Michael
authors: M
authors: Hanna
authors: Anne M
authors: AM
authors: Bowcock
authors: Pierre
authors: P
authors: Szepetowski
authors: Ying-Hui
authors: YH
authors: Fu
authors: Louis J
authors: LJ
authors: Ptáček
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004421:Dystonia / Q000150:complications* / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D012640:Seizures / Q000150:complications* / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human; D050825:Synaptosomal-Associated Protein 25