Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May;75(5):782-7.
doi: 10.1002/ana.24126. Epub 2014 Apr 14.

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

Ingrid E Scheffer  1 , 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
Affiliations

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

Ingrid E Scheffer et al. Ann Neurol. 2014 May.

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

  • Epileptic spasms are a feature of DEPDC5 mTORopathy.
    Carvill GL, Crompton DE, Regan BM, McMahon JM, Saykally J, Zemel M, Schneider AL, Dibbens L, Howell KB, Mandelstam S, Leventer RJ, Harvey AS, Mullen SA, Berkovic SF, Sullivan J, Scheffer IE, Mefford HC. Carvill GL, et al. Neurol Genet. 2015 Jul 23;1(2):e17. doi: 10.1212/NXG.0000000000000016. eCollection 2015 Aug. Neurol Genet. 2015. PMID: 27066554 Free PMC article.
  • Focal Cortical Dysplasia.
    Crino PB. Crino PB. Semin Neurol. 2015 Jun;35(3):201-8. doi: 10.1055/s-0035-1552617. Epub 2015 Jun 10. Semin Neurol. 2015. PMID: 26060899 Free PMC article. Review.
  • Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia.
    D'Gama AM, Geng Y, Couto JA, Martin B, Boyle EA, LaCoursiere CM, Hossain A, Hatem NE, Barry BJ, Kwiatkowski DJ, Vinters HV, Barkovich AJ, Shendure J, Mathern GW, Walsh CA, Poduri A. D'Gama AM, et al. Ann Neurol. 2015 Apr;77(4):720-5. doi: 10.1002/ana.24357. Epub 2015 Feb 26. Ann Neurol. 2015. PMID: 25599672 Free PMC article.
  • A novel variation in DEPDC5 causing familial focal epilepsy with variable foci.
    Wang Y, Niu W, Shi H, Bao X, Liu Y, Lu M, Sun Y. Wang Y, et al. Front Genet. 2024 Jun 21;15:1414259. doi: 10.3389/fgene.2024.1414259. eCollection 2024. Front Genet. 2024. PMID: 38974383 Free PMC article.
  • Pharmacogenomics in epilepsy.
    Balestrini S, Sisodiya SM. Balestrini S, et al. Neurosci Lett. 2018 Feb 22;667:27-39. doi: 10.1016/j.neulet.2017.01.014. Epub 2017 Jan 10. Neurosci Lett. 2018. PMID: 28082152 Free PMC article. Review.
See all "Cited by" articles

Publication types

LinkOut - more resources