TY - JOUR T1 - Targeted genomic sequencing identifies <em>PRRT2</em> mutations as a cause of paroxysmal kinesigenic choreoathetosis JF - Journal of Medical Genetics JO - J Med Genet SP - 76 LP - 78 DO - 10.1136/jmedgenet-2011-100635 VL - 49 IS - 2 AU - Jingyun Li AU - Xilin Zhu AU - Xin Wang AU - Wei Sun AU - Bing Feng AU - Te Du AU - Bei Sun AU - Fenghe Niu AU - Hua Wei AU - Xiaopan Wu AU - Lei Dong AU - Liping Li AU - Xingqiu Cai AU - Yuping Wang AU - Ying Liu Y1 - 2012/02/01 UR - http://jmg.bmj.com/content/49/2/76.abstract N2 - Background 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.Methods/results 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.Conclusion The present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous. ER -