Paroxysmal kinesigenic choreoathetosis (PKC): confirmation of linkage to 16p11-q21, but unsuccessful detection of mutations among 157 genes at the PKC-critical region in seven PKC families

Kikuchi, Taeko; Nomura, Masayo; Tomita, Hiroaki; Harada, Naoki; Kanai, Kazuaki; Konishi, Tomokazu; Yasuda, Akihiro; Matsuura, Masato; Kato, Nobuo; Yoshiura, Koh Ichiro; Niikawa, Norio

doi:10.1007/s10038-007-0116-7

Cited by 43 publications

(26 citation statements)

References 17 publications

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“…[2][3][4] In our previous study, we performed a genome-wide linkage and haplotype analysis and defined disease locus within the pericentromeric region of chromosome 16. 1,5 Subsequently, we performed mutation analysis on 229 genes between D16S3131 and D16S503; however, we failed to identify the causative gene. 5,6 Recently, Chen et al 7 identified truncating mutations within protein-rich transmembrane protein 2 (PRRT2) in eight HanChinese families with histories of PKD using whole-exome sequencing.…”

Section: Introductionmentioning

confidence: 99%

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Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions

et al. 2012

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Paroxysmal kinesigenic dyskinesia (PKD (MIM128000)) is a neurological disorder characterized by recurrent attacks of involuntary movements. Benign familial infantile convulsion (BFIC) is also one of a neurological disorder characterized by clusters of epileptic seizures. The BFIC1 (MIM601764), BFIC2 (MIM605751) and BFIC4 (MIM612627) loci have been mapped to chromosome 19q, 16p and 1p, respectively, while BFIC3 (MIM607745) is caused by mutations in SCN2A on chromosome 2q24. Furthermore, patients with BFIC have been observed in a family concurrently with PKD. Both PKD and BFIC2 are heritable paroxysmal disorders and map to the same region on chromosome 16. Recently, the causative gene of PKD, the protein-rich transmembrane protein 2 (PRRT2), has been detected using whole-exome sequencing. We performed mutation analysis of PRRT2 by direct sequencing in 81 members of 17 families containing 15 PKD families and two BFIC families. Direct sequencing revealed that two mutations, c.649dupC and c.748C4T, were detected in all members of the PKD and BFIC families. Our results suggest that BFIC2 is caused by a truncated mutation that also causes PKD. Thus, PKD and BFIC2 are genetically identical and may cause convulsions and involuntary movements via a similar mechanism.

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Section: Introductionmentioning

confidence: 99%

“…1,5 Subsequently, we performed mutation analysis on 229 genes between D16S3131 and D16S503; however, we failed to identify the causative gene. 5,6 Recently, Chen et al 7 identified truncating mutations within protein-rich transmembrane protein 2 (PRRT2) in eight HanChinese families with histories of PKD using whole-exome sequencing.…”

Section: Introductionmentioning

confidence: 99%

Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions

et al. 2012

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“…Further studies narrowed down the critical region for PKD/ ICCA. However, conventional genetic methods including linkage and haplotype analysis as well as Sanger sequencing of more than 150 genes located around the critical region in chromosome 16 were not able to identify the associated gene [ 25 ]. Only with the advent of whole-exome sequencing it was possible to demonstrate heterozygous mutations in PRRT2 as a cause of PKD [ 26 -29 ].…”

Section: Genetics Of Pkdmentioning

confidence: 99%

Genetics of Paroxysmal Dyskinesia

Brockmann

Rosewich

2015

Movement Disorder Genetics

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Paroxysmal dyskinesias (PxDs) constitute a clinically and genetically heterogeneous group of rare conditions characterized by recurrent brief episodes of abnormal involuntary movements. PxDs may present with episodic choreic, ballistic, athetoid features or any mixture of dystonic symptoms. Current classifi cation of PxDs based on different precipitating factors recognizes three subtypes including paroxysmal kinesigenic (PKD), nonkinesigenic (PNKD), and exercise-induced (PED) dyskinesia. Neurological examination between the attacks is usually normal in these subtypes. However, PxDs occur as a distinct feature of complex chronic neurological disorders, comprising Glut1 defi ciency syndrome, MCT8 defi ciency (Allen-Herndon-Dudley syndrome), and ATP1A3-related conditions (alternating hemiplegia of childhood; rapid-onset dystonia-parkinsonism). Alliance of meticulous phenotyping with state-of-the-art methods of molecular genetics resulted in new insights concerning the genetic causes of PxDs.

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“…Despite the identification of the chromosome 16 BFIE/ICCA/PKD locus in 1997 and the subsequent extensive sequencing of candidate genes within the region,19 21 the causative gene was not identified for many years. In 2011, Chen and colleagues4 successfully employed a strategy combining linkage analysis and whole exome sequencing to identify mutations in an uncharacterised gene, PRRT2 , in eight Chinese families with PKD.…”

Section: Identification Of Mutations In Prrt2mentioning

confidence: 99%

Role ofPRRT2in common paroxysmal neurological disorders: a gene with remarkable pleiotropy

Heron

Dibbens

2013

J Med Genet

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Mutations in the gene PRRT2 encoding proline-rich transmembrane protein 2 have recently been identified as the cause of three clinical entities: benign familial infantile epilepsy (BFIE), infantile convulsions with choreoathetosis (ICCA) syndrome, and paroxysmal kinesigenic dyskinesia (PKD). Patients with ICCA have both BFIE and PKD and families with ICCA may contain individuals who exhibit all three phenotypes. These three phenotypes were all mapped by linkage analyses to the pericentromeric region of chromosome 16, and were hypothesised to have the same genetic basis due to the co-occurrence of the disorders in some families. Despite considerable effort, the gene or genes for BFIE, ICCA, and PKD were not identified for many years after the linkage region was identified. Mutations in the gene PRRT2 were identified in several Chinese families with PKD, suggesting that the gene may also be responsible for ICCA and BFIE in families linked to the chromosome 16 locus. This was demonstrated to be the case, with the majority of families with ICCA and BFIE found to have PRRT2 mutations. The vast majority of these mutations are truncating and are predicted to lead to haploinsufficiency. PRRT2 is a largely uncharacterised protein. It is expressed in the brain and has been demonstrated to interact with SNAP-25, a component of the molecular machinery involved in the release of neurotransmitters at the presynaptic membrane. Therefore, the PRRT2 protein may play a role in this process. However, the molecular mechanisms underlying the remarkable pleiotropy associated with PRRT2 mutations have still to be determined.

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Paroxysmal kinesigenic choreoathetosis (PKC): confirmation of linkage to 16p11-q21, but unsuccessful detection of mutations among 157 genes at the PKC-critical region in seven PKC families

Cited by 43 publications

References 17 publications

Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions

Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions

Genetics of Paroxysmal Dyskinesia

Role ofPRRT2in common paroxysmal neurological disorders: a gene with remarkable pleiotropy

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