Infantile convulsions and paroxysmal kinesigenic dyskinesia with 16p11.2 microdeletion.
ABSTRACT Paroxysmal kinesigenic dyskinesia (PKD) is a rare paroxysmal movement disorder characterized by involuntary movements triggered by sudden voluntary movements.(1) PKD is a genetic disorder due to de novo mutations or autosomal dominant pedigree inheritance. Genetic linkage studies have generally localized the dominant gene to the pericentromic region of chromosome 16 (16p11-q21).(2) Despite extensive searching, including mutation analysis of 157 genes in this region, the PKD gene remains unidentified.(2).
Article: Mild paroxysmal kinesigenic dyskinesia caused by PRRT2 missense mutation with reduced penetrance.[show abstract] [hide abstract]
ABSTRACT: Paroxysmal kinesigenic dyskinesia (PKD) is an uncommon disorder characterized by brief episodes of involuntary dystonia or choreoathetosis triggered by sudden voluntary movement.(1) Recently, several groups identified mutations in patients with PKD in the proline-rich transmembrane protein 2 (PRRT2) gene.(2-7) We report a missense c.913G>A (p.Gly305Arg) change in PRRT2 in 4 siblings with PKD, 2 with infrequent symptoms. The association of a milder phenotype and reduced penetrance with this missense mutation suggests partial loss of function.Neurology 08/2012; 79(9):946-8. · 8.31 Impact Factor
Article: Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis.[show abstract] [hide abstract]
ABSTRACT: Paroxysmal kinesigenic choreoathetosis (PKC) is characterised by recurrent and brief attacks of involuntary movement, inherited as an autosomal dominant trait with incomplete penetrance. A PKC locus has been previously mapped to the pericentromeric region of chromosome 16 (16p11.2-q12.1), but the causative gene remains unidentified. Deep sequencing of this 30 Mb region enriched with array capture in five affected individuals from four Chinese PKC families detected two heterozygous PRRT2 insertions (c.369dupG and c.649dupC), producing frameshifts and premature stop codons (p.S124VfsX10 and p.R217PfsX8, respectively) in two different families. Sanger sequencing confirmed these two mutations and revealed a missense PRRT2 mutation (c.859G→A, p.A287T) in one of the two remaining families. This study also sequenced PRRT2 in 29 sporadic cases affected with PKC and identified mutations in 10 cases, including six with the c.649dupC mutation. Most variants were truncating mutations, consistent with loss-of-function and haploinsufficiency. The present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous.Journal of Medical Genetics 11/2011; 49(2):76-8. · 6.36 Impact Factor