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. 2012 Feb;49(2):76-8.
doi: 10.1136/jmedgenet-2011-100635. Epub 2011 Nov 30.

Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis

Jingyun Li  1 , Xilin Zhu, Xin Wang, Wei Sun, Bing Feng, Te Du, Bei Sun, Fenghe Niu, Hua Wei, Xiaopan Wu, Lei Dong, Liping Li, Xingqiu Cai, Yuping Wang, Ying Liu
Affiliations

Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis

Jingyun Li et al. J Med Genet. 2012 Feb.

Abstract

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.

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Conflict of interest statement

Competing interests: None.

Figures

Figure 1
Figure 1
Identified mutations in the PRRT2 gene. Relative positions of mutations are indicated by symbols. Red Stars, frameshift insertions; green triangles, frameshift deletions; black dots, missense; yellow triangles, splice site mutations.
See this image and copyright information in PMC

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