PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome

Sarah E. Heron; Bronwyn E. Grinton; Sara Kivity; Zaid Afawi; Sameer M. Zuberi; James N. Hughes; Clair Pridmore; Bree L. Hodgson; Xenia Iona; Lynette G. Sadleir; James Pelekanos; Eric Herlenius; Hadassa Goldberg-Stern; Haim Bassan; Eric Haan; Amos D. Korczyn; Alison E. Gardner; Mark A. Corbett; Jozef Gécz; Paul Q. Thomas; John C. Mulley; Samuel F. Berkovic; Ingrid E. Scheffer; Leanne M. Dibbens

doi:10.1016/j.ajhg.2011.12.003

PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome

Sarah E. Heron, Bronwyn E. Grinton, Sara Kivity, Zaid Afawi, Sameer M. Zuberi, James N. Hughes, Clair Pridmore, Bree L. Hodgson, Xenia Iona, Lynette G. Sadleir, James Pelekanos, Eric Herlenius, Hadassa Goldberg-Stern, Haim Bassan, Eric Haan, Amos D. Korczyn, Alison E. Gardner, Mark A. Corbett, Jozef Gécz, Paul Q. ThomasJohn C. Mulley, Samuel F. Berkovic, Ingrid E. Scheffer, Leanne M. Dibbens

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Abstract

Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).

Original language	English
Pages (from-to)	152-160
Number of pages	9
Journal	American Journal of Human Genetics
Volume	90
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2011.12.003
Publication status	Published or Issued - 13 Jan 2012

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Heron, S. E., Grinton, B. E., Kivity, S., Afawi, Z., Zuberi, S. M., Hughes, J. N., Pridmore, C., Hodgson, B. L., Iona, X., Sadleir, L. G., Pelekanos, J., Herlenius, E., Goldberg-Stern, H., Bassan, H., Haan, E., Korczyn, A. D., Gardner, A. E., Corbett, M. A., Gécz, J., ... Dibbens, L. M. (2012). PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. American Journal of Human Genetics, 90(1), 152-160. https://doi.org/10.1016/j.ajhg.2011.12.003

@article{7fb5caca470140df9218ad2b1f6100e2,

title = "PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome",

abstract = "Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).",

author = "Heron, {Sarah E.} and Grinton, {Bronwyn E.} and Sara Kivity and Zaid Afawi and Zuberi, {Sameer M.} and Hughes, {James N.} and Clair Pridmore and Hodgson, {Bree L.} and Xenia Iona and Sadleir, {Lynette G.} and James Pelekanos and Eric Herlenius and Hadassa Goldberg-Stern and Haim Bassan and Eric Haan and Korczyn, {Amos D.} and Gardner, {Alison E.} and Corbett, {Mark A.} and Jozef G{\'e}cz and Thomas, {Paul Q.} and Mulley, {John C.} and Berkovic, {Samuel F.} and Scheffer, {Ingrid E.} and Dibbens, {Leanne M.}",

note = "Funding Information: We thank the patients and their families for their participation and cooperation in our research. We would like to thank Marta Bayly and Bev Johns for technical assistance. This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952 to S.F.B., I.E.S., L.M.D., P.Q.T., and J.G., Australia Fellowship 466671 to S.F.B., Senior Research Fellowship 508043 to J.G., Practitioner Fellowship 1006110 to I.E.S., and Training Fellowship 1016715 to S.E.H.) and SA Pathology. P.Q.T. is a Pfizer Australia Research Fellow. L.M.D. is an MS McLeod Research Fellow. ",

year = "2012",

month = jan,

day = "13",

doi = "10.1016/j.ajhg.2011.12.003",

language = "English",

volume = "90",

pages = "152--160",

journal = "American Journal of Human Genetics",

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Heron, SE, Grinton, BE, Kivity, S, Afawi, Z, Zuberi, SM, Hughes, JN, Pridmore, C, Hodgson, BL, Iona, X, Sadleir, LG, Pelekanos, J, Herlenius, E, Goldberg-Stern, H, Bassan, H, Haan, E, Korczyn, AD, Gardner, AE, Corbett, MA, Gécz, J , Thomas, PQ, Mulley, JC, Berkovic, SF, Scheffer, IE & Dibbens, LM 2012, 'PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome', American Journal of Human Genetics, vol. 90, no. 1, pp. 152-160. https://doi.org/10.1016/j.ajhg.2011.12.003

TY - JOUR

T1 - PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome

AU - Heron, Sarah E.

AU - Grinton, Bronwyn E.

AU - Kivity, Sara

AU - Afawi, Zaid

AU - Zuberi, Sameer M.

AU - Hughes, James N.

AU - Pridmore, Clair

AU - Hodgson, Bree L.

AU - Iona, Xenia

AU - Sadleir, Lynette G.

AU - Pelekanos, James

AU - Herlenius, Eric

AU - Goldberg-Stern, Hadassa

AU - Bassan, Haim

AU - Haan, Eric

AU - Korczyn, Amos D.

AU - Gardner, Alison E.

AU - Corbett, Mark A.

AU - Gécz, Jozef

AU - Thomas, Paul Q.

AU - Mulley, John C.

AU - Berkovic, Samuel F.

AU - Scheffer, Ingrid E.

AU - Dibbens, Leanne M.

N1 - Funding Information: We thank the patients and their families for their participation and cooperation in our research. We would like to thank Marta Bayly and Bev Johns for technical assistance. This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952 to S.F.B., I.E.S., L.M.D., P.Q.T., and J.G., Australia Fellowship 466671 to S.F.B., Senior Research Fellowship 508043 to J.G., Practitioner Fellowship 1006110 to I.E.S., and Training Fellowship 1016715 to S.E.H.) and SA Pathology. P.Q.T. is a Pfizer Australia Research Fellow. L.M.D. is an MS McLeod Research Fellow.

PY - 2012/1/13

Y1 - 2012/1/13

N2 - Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).

AB - Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).

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U2 - 10.1016/j.ajhg.2011.12.003

DO - 10.1016/j.ajhg.2011.12.003

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AN - SCOPUS:84855827661

VL - 90

SP - 152

EP - 160

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -

PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome

Abstract

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