PRRT2 mutations in Japanese patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia

Okumura, Akihisa; Shimojima, Keiko; Kurahashi, Hirokazu; Numoto, Shingo; Shimada, Shino; Ishii, Atsushi; Ohmori, Iori; Takahashi, Satoru; Awaya, Tomonari; Sakakibara, Takafumi; Ishihara, Naoko; Hattori, Ayako; Torisu, Hiroyuki; Tohyama, Jun; Inoue, Takeshi; Haibara, Akiko; Nishida, Takuji; Yuhara, Yukihiro; Miya, Kazushi; Tanaka, Ryuta; Hirose, Sachiko; Yamamoto, Toshiyuki

doi:10.1016/j.seizure.2019.05.017

Cited by 17 publications

(16 citation statements)

References 36 publications

(52 reference statements)

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“…Outcome of patients with PRRT2 -associated disorders is usually favorable. In the present study, the average age of remission of patients with BFIE was 8.5 ± 5.0 months, which was similar to previously published data ( 29 ). Most patients had normal psychomotor development at last follow-up.…”

Section: Discussionsupporting

confidence: 92%

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children

et al. 2021

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Objectives: To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 (PRRT2) gene-associated disorders.Methods: Targeted next generation sequencing (NGS) was used to identify pathogenic PRRT2 variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed PRRT2-associated disorders were monitored and their clinical data were analyzed.Results: Forty-four patients with pathogenic PRRT2 variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was de novo. Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, P = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability.Conclusion: Our data suggested that patients with whole gene deletions could have more severe manifestations in PRRT2-associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.

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Section: Discussionsupporting

confidence: 92%

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children

et al. 2021

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“…The double occurrence of PRRT2 mutations in a patient with PKD has been previously reported with intelligent disability [20]. While several studies reported that homozygous mutations cause sever neurological symptoms, recent reported c.981C>G homozygous mutation has not resulted in severe disorder [33]. Consistent with our result, this supports the hypothesis that differences in the epilepsy phenotypes in the patients with PRRT2 mutations depend on the types of PRRT2 mutations.…”

supporting

confidence: 92%

A Novel PRRT2 Variant in Chinese Patients Suffering from Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsion

Baldi

Zhu

Qing-yun

et al. 2020

Behavioural Neurology

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PRRT2 mutations are the major causative agent of paroxysmal kinesigenic dyskinesia with infantile convulsion (PKD/IC). The study is aimed at screening PRRT2 gene mutations in patients who suffered from PKD/IC in Chinese population. Thirteen Chinese patients with PKD/IC were screened randomly for coding exons of the PRRT2 gene mutation along with 50 ethnically coordinated control people. Nine (2 unaffected) and 4 of the patients showed familial PKD/IC and apparently sporadic cases, respectively. We identified 5 different PRRT2 mutations in 10 individuals, including 8 familial and 2 apparently sporadic cases. However, no mutations were found in the 50 ethnically matched controls. Unknown (novel) NM_145239.2:c.686G>A and previously reported NM_145239.2:c.743G>C variants were identified in two familial and sporadic patients. All affected members of family A showed mutation NM_145239.2:c.650_670delinsCAATGGTGCCACCACTGGGTTA. The previously identified NM_145239.2:c.412 C>G and NM_145239.2:c.709G>A variants are seen in two individuals assessed in family B. Other than the previously identified variants, some of the patients with PRRT2-PKD/IC showed a new PRRT2 substitution variant. Thus, the spectrum of PRRT2 variants is expanded. The possible role and probability of PRRT2 variants involved in PKD/IC are highlighted.

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“…Decreased nodal centrality in the MTG has also been reported in epilepsy (M. Liu, Chen, Beaulieu, & Gross, 2014), which may partly explain both the overlap of symptoms between PKD and epilepsy and the therapeutic effect of antiepileptic agents in PKD. It is also noteworthy that PRRT2 mutations were identified in both PKD patients and epilepsy patients (Okumura et al, 2019). We suggest that the nodal alterations in the temporal lobe observed only in PKD‐M patients may be induced by PRRT2 mutations.…”

Section: Discussionmentioning

confidence: 99%

Brain structural connectome in relation to PRRT2 mutations in paroxysmal kinesigenic dyskinesia

Lei

Suo

et al. 2020

Human Brain Mapping

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This study explored the topological characteristics of brain white matter structural networks in patients with Paroxysmal Kinesigenic Dyskinesia (PKD), and the potential influence of the brain network stability gene PRRT2 on the structural connectome in PKD. Thirty‐five PKD patients with PRRT2 mutations (PKD‐M), 43 PKD patients without PRRT2 mutations (PKD‐N), and 40 demographically‐matched healthy control (HC) subjects underwent diffusion tensor imaging. Graph theory and network‐based statistic (NBS) approaches were performed; the topological properties of the white matter structural connectome were compared across the groups, and their relationships with the clinical variables were assessed. Both disease groups PKD‐M and PKD‐N showed lower local efficiency (implying decreased segregation ability) compared to the HC group; PKD‐M had longer characteristic path length and lower global efficiency (implying decreased integration ability) compared to PKD‐N and HC, independently of the potential effects of medication. Both PKD‐M and PKD‐N had decreased nodal characteristics in the left thalamus and left inferior frontal gyrus, the alterations being more pronounced in PKD‐M patients, who also showed abnormalities in the left fusiform and bilateral middle temporal gyrus. In the connectivity characteristics assessed by NBS, the alterations were more pronounced in the PKD‐M group versus HC than in PKD‐N versus HC. As well as the white matter alterations in the basal ganglia‐thalamo‐cortical circuit related to PKD with or without PRRT2 mutations, findings in the PKD‐M group of weaker small‐worldness and more pronounced regional disturbance show the adverse effects of PRRT2 gene mutations on brain structural connectome.

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PRRT2 mutations in Japanese patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia

Cited by 17 publications

References 36 publications

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children

A Novel PRRT2 Variant in Chinese Patients Suffering from Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsion

Brain structural connectome in relation to PRRT2 mutations in paroxysmal kinesigenic dyskinesia

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