Medicine (Austin & Northern Health) - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/211

Filters

2014 - 2015 2
2
Reset filters

Settings
Statistics
Citations
Author: Berkovic, Samuel × Author: Crompton, Douglas × Author: Mandelstam, Simone × Start date: 2014 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    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 (LIPPINCOTT WILLIAMS & WILKINS, 2015-08)
    OBJECTIVE: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. METHODS: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. RESULTS: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. CONCLUSIONS: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies.
  • Item
    Thumbnail Image
    Mutations in Mammalian Target of Rapamycin Regulator DEPDC5 Cause Focal Epilepsy with Brain Malformations
    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 (WILEY-BLACKWELL, 2014-05)
    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.