title: Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia.
abstract: Paroxysmal dyskinesia (PxD) is a group of movement disorders characterized by recurrent episodes of involuntary movements. Familial paroxysmal kinesigenic dyskinesia (PKD) is caused by PRRT2 mutations, but a distinct etiology has been suggested for sporadic PKD. Here we describe a cohort of patients collected from our movement disorders outpatient clinic in the period 1996-2011. Fifteen patients with sporadic PxD and 23 subjects from three pedigrees with familial PKD were screened for mutations in candidate genes. PRRT2 mutations co-segregated with PKD in two families and occurred in two sporadic cases of PKD. No mutations were detected in patients with non-kinesigenic or exertion-induced dyskinesia, and none in other candidate genes including PNKD1 (MR-1) and SLC2A1 (GLUT1). Thus, PRRT2 mutations also cause sporadic PKD as might be expected given the variable expressivity and reduced penetrance observed in familial PKD. Further genetic heterogeneity is suggested by the absence of candidate gene mutations in both sporadic and familial PKD suggesting a contribution of other genes or non-coding regions.
authors: Departments of Clinical Genetics and Functional Genomics, Center of Neurogenomics and Cognitive Research (CNCR), VU University and VU Medical Center, Amsterdam, The Netherlands. a.j.a.groffen@vu.nl
authors: Alexander J A
authors: AJ
authors: Groffen
authors: Thom
authors: T
authors: Klapwijk
authors: Anne-Fleur
authors: AF
authors: van Rootselaar
authors: Justus L
authors: JL
authors: Groen
authors: Marina A J
authors: MA
authors: Tijssen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human