Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

Ingrid E. Scheffer; Sarah E. Heron; Brigid M. Regan; Simone Mandelstam; Douglas E. Crompton; Bree L. Hodgson; Laura Licchetta; Federica Provini; Francesca Bisulli; Lata Vadlamudi; Jozef Gecz; Alan Connelly; Paolo Tinuper; Michael G. Ricos; Samuel F. Berkovic; Leanne M. Dibbens

doi:10.1002/ana.24126

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

Ingrid E. Scheffer, Sarah E. Heron, Brigid M. Regan, Simone Mandelstam, Douglas E. Crompton, Bree L. Hodgson, Laura Licchetta, Federica Provini, Francesca Bisulli, Lata Vadlamudi, Jozef Gecz, Alan Connelly, Paolo Tinuper, Michael G. Ricos, Samuel F. Berkovic, Leanne M. Dibbens

Istituto Scienze Neurologiche

Research output: Contribution to journal › Article › peer-review

Abstract

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.

Original language	English
Pages (from-to)	782-787
Number of pages	6
Journal	Annals of Neurology
Volume	75
Issue number	5
DOIs	https://doi.org/10.1002/ana.24126
Publication status	Published - 2014

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Scheffer, I. E., Heron, S. E., Regan, B. M., Mandelstam, S., Crompton, D. E., Hodgson, B. L., Licchetta, L., Provini, F., Bisulli, F., Vadlamudi, L., Gecz, J., Connelly, A., Tinuper, P., Ricos, M. G., Berkovic, S. F., & Dibbens, L. M. (2014). Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Annals of Neurology, 75(5), 782-787. https://doi.org/10.1002/ana.24126

Scheffer, IE, Heron, SE, Regan, BM, Mandelstam, S, Crompton, DE, Hodgson, BL, Licchetta, L , Provini, F , Bisulli, F, Vadlamudi, L, Gecz, J, Connelly, A, Tinuper, P, Ricos, MG, Berkovic, SF & Dibbens, LM 2014, 'Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations', Annals of Neurology, vol. 75, no. 5, pp. 782-787. https://doi.org/10.1002/ana.24126

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title = "Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations",

abstract = "We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.",

author = "Scheffer, {Ingrid E.} and Heron, {Sarah E.} and Regan, {Brigid M.} and Simone Mandelstam and Crompton, {Douglas E.} and Hodgson, {Bree L.} and Laura Licchetta and Federica Provini and Francesca Bisulli and Lata Vadlamudi and Jozef Gecz and Alan Connelly and Paolo Tinuper and Ricos, {Michael G.} and Berkovic, {Samuel F.} and Dibbens, {Leanne M.}",

year = "2014",

doi = "10.1002/ana.24126",

language = "English",

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AU - Scheffer, Ingrid E.

AU - Heron, Sarah E.

AU - Regan, Brigid M.

AU - Mandelstam, Simone

AU - Crompton, Douglas E.

AU - Hodgson, Bree L.

AU - Licchetta, Laura

AU - Provini, Federica

AU - Bisulli, Francesca

AU - Vadlamudi, Lata

AU - Gecz, Jozef

AU - Connelly, Alan

AU - Tinuper, Paolo

AU - Ricos, Michael G.

AU - Berkovic, Samuel F.

AU - Dibbens, Leanne M.

PY - 2014

Y1 - 2014

N2 - We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.

AB - We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.

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JO - Annals of Neurology

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Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

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