<i>PRRT2</i>phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions

Vliet, Rianne van; Breedveld, Guido J.; Andel, Johanneke de Rijk-van; Brilstra, Eva H.; Verbeek, Nienke E.; Verschuuren‐Bemelmans, Corien C.; Boon, Maartje; Samijn, Johnny P.A.; Diderich, Karin E. M.; Laar, Ingrid M.B.H. van de; Oostra, Ben A.; Bonifati, Vincenzo; Maat‐Kievit, Anneke

doi:10.1212/wnl.0b013e3182661fe3

Cited by 81 publications

(75 citation statements)

References 33 publications

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“…The most common c.649_650insC mutation has been identified in a majority of families with BIE and/or PKD [4][5][6][7][9][10][11][12][13][16][17][18]. Age at the onset and offset of epilepsy was variable among individuals even within a single family with c.649_650insC mutation [5].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Heron et al identified five different mutations in PRRT2 in 14 of 17 families affected by BIE and in five of six families affected by ICCA [5] and Ono et al found two mutations in PRRT2, c.649_650insC and c.748C>T, in all individuals with PKD and/or BIE [6]. Thereafter, several reports have shown that PRRT2 mutation will be one of the major genes relating to BIE, PKD, and ICCA [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. However, we hypothesized that PRRT2 mutation may also be related to several phenotypes of infantile epilepsies other than BIE and/or PKD.…”

Section: Introductionmentioning

confidence: 99%

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PRRT2 mutation in Japanese children with benign infantile epilepsy

Okumura

Shimojima

Abe

et al. 2013

Brain and Development

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PRRT2 mutation in Japanese children with benign infantile epilepsy

Okumura

Shimojima

Abe

et al. 2013

Brain and Development

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“…The high prevalence of migraine in the general population may, however, explain why co-segregation is not always found [44].…”

Section: Familial Hmmentioning

confidence: 99%

PRRT2 mutations and paroxysmal disorders

Méneret

Gaudebout

Riant

et al. 2013

Euro J of Neurology

100

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In the past year, mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on PRRT2 mutation-associated disorders. Our objectives were to describe the wide clinical spectrum associated with PRRT2 mutations, and to present the current hypotheses on the underlying pathophysiology. PRRT2 mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The PRRT2 protein, through its interaction with SNAP-25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by PRRT2 loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age-dependent expression. The clinical spectrum of PRRT2 mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.

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“…Several of these mutations have been demonstrated to cause altered cellular localisation of the PRRT2 protein or loss of detectable protein expression in vitro 4 28. Fifteen different missense mutations have been reported 22–25 29 34 35 37 42 45 46 50 54. These alter amino acid residues clustered in and around two putative transmembrane domains located near the C-terminus of the protein (table 1, figure 2A).…”

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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PRRT2phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions

Cited by 81 publications

References 33 publications

PRRT2 mutation in Japanese children with benign infantile epilepsy

PRRT2 mutation in Japanese children with benign infantile epilepsy

PRRT2 mutations and paroxysmal disorders

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

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