PRRT2 mutation in Japanese children with benign infantile epilepsy

Okumura, Akihisa; Shimojima, Keiko; Abe, Shinpei; Yamashita, Shintaro; Imai, Katsumi; Okanishi, Tohru; Enoki, Hideo; Fukasawa, Toshio; Tanabe, Takuya; Dibbens, Leanne M.; Shimizu, Toshiaki; Yamamoto, Toshiyuki

doi:10.1016/j.braindev.2012.09.015

Cited by 35 publications

(34 citation statements)

References 27 publications

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“…Here we report the clinical features of familial cases with either BIC or PKD. The PRRT2 mutation identified in the present study has been reported in a patient with BIC without PKD [8]. …”

Section: Introductionsupporting

confidence: 62%

“…The PRRT2 missense mutation (c.981C > G, p.Ile327Met) was identified in two patients with BIC and three patients with PKD as well as in two unaffected individuals. The same PRRT2 mutation has been identified in a patient with BIC without PKD [8]. Allowing incomplete penetrance in the mutation carriers, this mutation co-segregated completely with the phenotype.…”

Section: Discussionmentioning

confidence: 73%

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Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic dyskinesia: a case series

et al. 2014

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IntroductionParoxysmal kinesigenic dyskinesia is characterized by sudden attacks of involuntary movements. It is often misdiagnosed clinically as psychogenic illness, which distresses the patients to a great extent. A correct diagnosis will improve the quality of life in patients with paroxysmal kinesigenic dyskinesia because treatment with low doses of anticonvulsants is effective for eliminating the clinical manifestations. Paroxysmal kinesigenic dyskinesia can occur independently of or concurrently with benign infantile convulsion. Identification of PRRT2 as the causative gene of benign infantile convulsion and paroxysmal kinesigenic dyskinesia allows genetic confirmation of the clinical diagnosis.Case presentationWe describe the clinical features of a Japanese family with either paroxysmal kinesigenic dyskinesia or benign infantile convulsion. A PRRT2 missense mutation (c.981C > G, p.Ile327Met) was identified in two patients with benign infantile convulsion and three patients with paroxysmal kinesigenic dyskinesia as well as in two unaffected individuals. Allowing incomplete penetrance in the mutation carriers, this mutation co-segregated completely with the phenotype. The patients with paroxysmal kinesigenic dyskinesia had been misdiagnosed with psychogenic illness for many years. They were correctly diagnosed with paroxysmal kinesigenic dyskinesia when their children visited a pediatrician for benign infantile convulsion. Treatment with carbamazepine controlled their involuntary movements completely.ConclusionsParoxysmal kinesigenic dyskinesia is a treatable movement disorder that is often misdiagnosed clinically as psychogenic illness. It is important to note that two clinically distinct disorders, benign infantile convulsion and paroxysmal kinesigenic dyskinesia, are allelic conditions caused by PRRT2 mutations. Paroxysmal kinesigenic dyskinesia should be suspected in families with a child with benign infantile convulsion.

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“…Here we report the clinical features of familial cases with either BIC or PKD. The PRRT2 mutation identified in the present study has been reported in a patient with BIC without PKD [8]. …”

Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 73%

Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic dyskinesia: a case series

et al. 2014

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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%

“…PRRT2 mutations have not been associated with other phenotypes that include infantile seizures. In particular, no mutations have been identified in patients with convulsions with gastroenteritis (CwG) or benign familial neonatal epilepsy (BFNE) 43 48 50. BFNE is most commonly caused by mutations in the potassium channel subunit genes KCNQ2 and KCNQ3 61.…”

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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“…PRRT2 mutation is the major cause of PKD in Chinese, Koreans, Japanese, and Europeans [7][8][9][10][11] and accounts for 33% to 46% of sporadic and 80% to 100% of familial forms of PKD. 12 Heterozygous c.649dupC is a mutation hotspot of which the mutation detection rate for Chinese can be as high as 62%.…”

Section: Discussionmentioning

confidence: 99%

A common PRRT2 mutation in familial paroxysmal kinesigenic dyskinesia in Hong Kong: a case series of 16 patients

et al. 2016

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Patient 1 was a 47-year-old woman who presented with paroxysmal abnormal movement since childhood. She was first seen in 2004. The attack was characterised by dystonic painful posture with upward or downward deviation of the eyes, head turning, shoulder abduction and extensions, lower limb dystonia, impaired speech, and occasionally stepping movements, with preserved consciousness. The attacks lasted for 1 to 2 minutes with a frequency of up to 8 times a day. Each attack was precipitated by stress or being startled, for example, being approached by a car unexpectedly when crossing the road, frightened by a cockroach, a sudden phone call, or an abrupt movement. Occasionally, the attack could occur during sleep. There was no incontinence. The patient had normal intelligence. Physical examination, biochemical tests, computed tomography of the brain, and electroencephalography were normal. The attacks were controlled with carbamazepine and frequency of attacks reduced to fewer than 3 times a day and each episode was shortened to 10 to 20 seconds. The patient also had a history of seizure of unknown aetiology in childhood. She had a strong family history; her daughter has presented with seizure on two to three occasions since the age of 10 months and had been taking an anticonvulsant for 2 years. Since then she had experienced no further seizures and by the age of 4 years no antiepileptic drug or follow-up has been required. Two older sisters and a nephew of the proband also had childhood seizures. Family 2Patient 2 was a 26-year-old woman who presented with paroxysmal kinesigenic dyskinesia (PKD) since the age of 8 years. The patient first presented with episodes of afebrile seizure at 7 months old in 1997. She was prescribed phenobarbitone and required no further medication or follow-up after the age of 3 years. The current involuntary movement affected all limbs with the right side being most affected. Each attack lasted for a few seconds to less than 3 minutes without loss of consciousness. Each episode was triggered by sudden body movement, anxiety, or deprived sleep. Frequency of attacks could reach up to 6 times a day. The patient claimed she could occasionally partially control the symptoms. Physical examination, biochemical tests, and brain imaging were unremarkable. Her brother was also affected by PKD. The attack was controlled by carbamazepine; a missed dose would usually lead to relapse. Family 3Patient 3 was a 14-year-old boy who presented in 2004 with chorea-like movement of the four limbs since the age of 18 months. Each attack lasted for about 15 to 20 seconds and there was no impaired consciousness. The frequency of attacks could reach up to 10 times a day. The attacks were triggered after running or waking up from sleep. A good clinical response was achieved with carbamazepine. The attacks recurred only after a missed dose. Physical examination, biochemical investigations, and brain imaging were unremarkable and he had normal development and intelligence. Five paternal family CASE REPORT

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PRRT2 mutation in Japanese children with benign infantile epilepsy

Cited by 35 publications

References 27 publications

Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic dyskinesia: a case series

Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic dyskinesia: a case series

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

A common PRRT2 mutation in familial paroxysmal kinesigenic dyskinesia in Hong Kong: a case series of 16 patients

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