Dataset Information

Intronic PRRT2 mutation generates novel splice acceptor site and causes paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) in a three generation family.

ABSTRACT: Mutations in PRRT2 cause autosomal dominant paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC).A previously not recognized intronic PRRT2 mutation (c.880-35G > A; p.S294Lfs*29) was found in an 18 month old girl with IC and in her mother with classical presentation of PKD. The mutation results in a novel splice acceptor site in intron 2 of PRRT2. Due to frameshift and a subsequent premature stop-codon the resulting transcript appears to render the PRRT2 protein non/dysfunctional and is the likely cause of disease in this family.Our findings expand the mutational spectrum of this disease.

SUBMITTER: Weber A

PROVIDER: S-EPMC4776392 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Intronic PRRT2 mutation generates novel splice acceptor site and causes paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) in a three generation family.

Weber Axel A Kreth Jonas J Müller Ulrich U

BMC medical genetics 20160303

<h4>Background</h4>Mutations in PRRT2 cause autosomal dominant paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC).<h4>Case presentation</h4>A previously not recognized intronic PRRT2 mutation (c.880-35G > A; p.S294Lfs*29) was found in an 18 month old girl with IC and in her mother with classical presentation of PKD. The mutation results in a novel splice acceptor site in intron 2 of PRRT2. Due to frameshift and a subsequent premature stop-codon the resulting transcript appears ...[more]

PMID: 26936445

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Project description:BackgroundParoxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (PRRT2) are the most common genetic cause of PKD.ObjectiveThe objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.MethodsWe enrolled 219 PKD patients, documented their clinical information and performed PRRT2 screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without PRRT2 variants. Genotype-phenotype correlation analyses were conducted on the probands.ResultsAmong 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 PRRT2 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without PRRT2 variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% versus 8.99%, respectively). Patients with truncated PRRT2 variants tend to have bilateral attacks. We identified two transmembrane protein 151A (TMEM151A) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.ConclusionThese findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated PRRT2 variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of PRRT2 and TMEM151A variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.

Dataset Information

Intronic PRRT2 mutation generates novel splice acceptor site and causes paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) in a three generation family.

Publications

Intronic PRRT2 mutation generates novel splice acceptor site and causes paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) in a three generation family.

Similar Datasets

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