Localization and Mutation Detection for Paroxysmal Kinesigenic Choreoathetosis

Du, Tian; Bao, Feng; Wang, Xin; Mao, Wei; Zhu, Xilin; Li, Liping; Sun, Bei; Niu, Nifang; Liu, Yang; Wang, Yuping; Chen, Biao; Cai, Xingqiu; Liu, Ying

doi:10.1007/s12031-007-9012-z

Cited by 8 publications

(5 citation statements)

References 19 publications

(21 reference statements)

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“…We previously performed linkage and haplotype analysis in four Chinese families (family 2 and family 4 with incomplete penetrance) with similar choreoathetosis clinical symptoms, and all mapped the disease locus to a region between D16S3093 and D16S3057 at 16p11.2-q12.1 2 3. This PKC critical region was in accordance with other studies 4 5.…”

Section: Introductionsupporting

confidence: 80%

Targeted genomic sequencing identifiesPRRT2mutations as a cause of paroxysmal kinesigenic choreoathetosis

Zhu

Wang

et al. 2011

J Med Genet

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BackgroundParoxysmal 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/resultsDeep 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.ConclusionThe present study identifies PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is genetically heterogeneous.

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Section: Introductionsupporting

confidence: 80%

Targeted genomic sequencing identifiesPRRT2mutations as a cause of paroxysmal kinesigenic choreoathetosis

Zhu

Wang

et al. 2011

J Med Genet

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“…Chorea and choreoathetosis were more frequent. Detailed clinical manifestations were reported elsewhere [16].…”

Section: Resultsmentioning

confidence: 99%

“…We previously performed a linkage and haplotype analysis on one Chinese PKC family (Family 2) [16]. A maximal two‐point logarithm of odds (LOD) score of 1.21 was obtained in D16S3081.…”

Section: Introductionmentioning

confidence: 99%

Paroxysmal kinesigenic choreoathetosis: evidence of linkage to the pericentromeric region of chromosome 16 in four Chinese families

Wang

Sun

Zhu

et al. 2010

Euro J of Neurology

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“…The nature of the infantile convulsions and the paroxysmal dyskinesias has been well described (Bruno et al, 2004; Rochette et al, 2008; Swoboda et al, 2000; Szepetowski et al, 1997). The gene for PKD/IC has been mapped to chromosome 16 by many groups and extensive efforts to identify the gene have been ongoing (Bennett et al, 2000; Callenbach et al, 2005; Caraballo et al, 2001; Du et al, 2008; Kikuchi et al, 2007; Lee et al, 1998; Roll et al; Swoboda et al, 2000; Szepetowski et al, 1997; Tomita et al, 1999; Weber et al, 2004). …”

Section: Introductionmentioning

confidence: 99%

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

Lee¹,

Huang²,

Bruneau³

et al. 2012

Cell Reports

242

224

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Summary Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions (PKD/IC) is an episodic movement disorder with autosomal dominant inheritance and high penetrance, but the causative gene is unknown. We have now identified four truncating mutations involving the PRRT2 gene in the vast majority (24/25) of well characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. The PRRT2 gene encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture and mutants associated with PKD/IC lead to dramatically reduced PRRT2 protein levels leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

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Localization and Mutation Detection for Paroxysmal Kinesigenic Choreoathetosis

Abstract: The culprit gene for PKC was located in approximately 19.34 cM region between 16p12.1-q13, and CACNG3, IL4R and ABCC11 were all ruled out as the cause.

Cited by 8 publications

References 19 publications

Targeted genomic sequencing identifiesPRRT2mutations as a cause of paroxysmal kinesigenic choreoathetosis

Targeted genomic sequencing identifiesPRRT2mutations as a cause of paroxysmal kinesigenic choreoathetosis

Paroxysmal kinesigenic choreoathetosis: evidence of linkage to the pericentromeric region of chromosome 16 in four Chinese families

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

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