TY - JOUR
T1 - Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia
AU - Groffen, Alexander J.A.
AU - Klapwijk, Thom
AU - Van Rootselaar, Anne Fleur
AU - Groen, Justus L.
AU - Tijssen, Marina A.J.
N1 - Funding Information: We are grateful to patients and families who participated in the study. Zabiollah Abbas is acknowledged for expert technical assistance. This work was supported by the Prinses Beatrix Foundation (WAR08-07 to Groffen). Tijssen received support from the Prinses Beatrix Foundation, STW Technology society program: Perspective–NeuroSIPE the ONWA Graduate School of Neurosciences Amsterdam and Ipsen Farmaceutics. Groen received an AMC Graduate School Scholarship.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
KW - Benign familial neonatal convulsions
KW - Infantile convulsions and paroxysmal choreoathetosis
KW - Migraine
KW - Paroxysmal kinesigenic dyskinesia
UR - http://www.scopus.com/inward/record.url?scp=84872300427&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00415-012-6592-5
DO - https://doi.org/10.1007/s00415-012-6592-5
M3 - Article
C2 - 22752065
SN - 0340-5354
VL - 260
SP - 93
EP - 99
JO - Journal of neurology
JF - Journal of neurology
IS - 1
ER -