Mutations in<i>PRRT2</i>result in paroxysmal dyskinesias with marked variability in clinical expression

Liu, Qing; Zhan, Qi; Wan, Xinhua; Li, Jingyun; Shi, Lei; Lü, Qiang; Zhou, Xiya; Li, Qiao; Wu, Liwen; Liu, Xiuqin; Yang, Wei; Liu, Ying; Cui, Liying; Zhang, Xue

doi:10.1136/jmedgenet-2011-100653

Cited by 90 publications

(110 citation statements)

References 19 publications

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“…The c.649dupC mutation identified in the family with BFIS and hemiplegic migraine was also identified in 5 other families in our series (figure 2) and in several already published families. [10][11][12][13][14] However, hemiplegic migraine was present only in this family (figure 2, family 11), possibly suggesting an interfamilial phenotypic variability and the interaction of PRRT2 with genetic modifiers.…”

mentioning

confidence: 79%

“…The p.Arg217-Profs*8 is a recurrent frameshift, loss of function mutation 13 that has also been identified in families and in sporadic patients with paroxysmal kinesigenic dyskinesias with or without infantile convulsions and benign familial infantile epilepsy. [9][10][11][12][13][14] The analysis of additional BFIS families led us to identify the c.649dupC in 3 additional familial cases and in the 2 sporadic cases (table, figure 2). In one of the 2 sporadic patients, the mutation occurred de novo.…”

mentioning

confidence: 99%

“…2 The p.Arg217Profs*8 mutation, which is a loss of function mutation, 13 is emerging as a very recurrent mutation in patients with paroxysmal kinesigenic dyskinesia, with or without infantile convulsions and BFIS. [10][11][12][13][14] After identifying the c.649dupC mutation in family 1, we assembled and studied a cohort of 32 probands with BFIS, ICCA, and other idiopathic infantile seizures, either familial or sporadic, and identified PRRT2 mutations in 10 additional probands (11/33; 33%). Family history revealed that 8 probands had a familial segregation: 5 had pure BFIS, 1 had ICCA, 1 had a cooccurrence of BFIS and childhood absence epilepsy, 1 had a cosegregation of BFIS and hemiplegic migraine, and 2 had a combination of BFIS, febrile seizures, paroxysmal dyskinesia, and migraine.…”

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confidence: 99%

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PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine

et al. 2012

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Objective: To perform a clinical and genetic study of a family with benign familial infantile seizures (BFIS) and, upon finding a PRRT2 gene mutation, to study a cohort of probands with a similar phenotype. We extended the study to all available family members to find out whether PRRT2 mutations cosegregated with additional symptoms. Methods:We carried out a clinical and genealogic study of a 3-generation family and of 32 additional probands with BFIS (11 families), infantile convulsions and paroxysmal choreoathetosis (ICCA) (9 families), BFIS/generalized epilepsy with febrile seizures plus (5 families), and sporadic benign neonatal or infantile seizures (7 probands/families). We performed a genetic study consisting of linkage analysis and PRRT2 screening of the 33 probands/families. Results:We obtained a positive linkage in the 16p11.3-q23.1 chromosomal region in the large BFIS family. Mutation analysis of PRRT2 gene revealed a c.649dupC (p.Arg217Profs*8) in all affected individuals. PRRT2 analysis of the 32 additional probands showed mutations in 10, 8 familial and 2 sporadic, probands. Overall we found PRRT2 mutations in 11 probands with a mutation rate of 11 out of 33 (33%). BFIS co-occurred with migraine and febrile seizures in 2 families, with childhood absence epilepsy in one family and with hemiplegic migraine in one family. Conclusion:Our results confirm the predominant role of PRRT2 mutations in BFIS and expand the spectrum of PRRT2-associated phenotypes to include febrile seizures, childhood absence seizures, migraine, and hemiplegic migraine.

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confidence: 99%

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PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine

et al. 2012

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“…Sanger sequencing of PRRT2 revealed the recognized pathogenic (c.649_650InsC p.P217fsX7) heterozygous mutation [2][3][4][5][6][7] in all eight clinically affected individuals as well as in three of the seven clinically unaffected individuals (Fig. 1).…”

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confidence: 99%

“…Attacks usually respond to low-dose carbamazepine [1]. Mutations in PRRT2 have been identified as a cause of autosomal dominant PKD [2] and replicated in other studies [3][4][5][6][7]. It remains important to report the clinical characteristics of genetically defined families in order to fully describe the clinical syndrome, including the presence of additional associated features beyond the movement disorder.…”

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confidence: 99%

Migraine with aura as the predominant phenotype in a family with a PRRT2 mutation

Sheerin¹,

Stamelou²,

Charlesworth³

et al. 2012

J Neurol

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Paroxysmal motor disorders: expanding phenotypes lead to coalescing genotypes

Zima

Ceulemans

Reiner

et al. 2018

Ann Clin Transl Neurol

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Paroxysmal movement disorders encompass varied motor phenomena. Less recognized features and wide phenotypic and genotypic heterogeneity are impediments to straightforward molecular diagnosis. We describe a family with episodic ataxia type 1, initially mis‐characterized as paroxysmal dystonia to illustrate this diagnostic challenge. We summarize clinical features in affected individuals to highlight underappreciated aspects and provide comprehensive phenotypic description of the rare familial KCNA1 mutation. Delayed diagnosis in this family is emblematic of the broader challenge of diagnosing other paroxysmal motor disorders. We summarize genotypic and phenotypic overlap and provide a suggested diagnostic algorithm for approaching patients with these conditions.

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Mutations inPRRT2result in paroxysmal dyskinesias with marked variability in clinical expression

Cited by 90 publications

References 19 publications

PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine

PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine

Migraine with aura as the predominant phenotype in a family with a PRRT2 mutation

Paroxysmal motor disorders: expanding phenotypes lead to coalescing genotypes

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