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Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy.
van Kranenburg, Melissa; Hoogeveen-Westerveld, Marianne; Nellist, Mark.
Affiliation
  • van Kranenburg M; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Hum Mutat ; 36(2): 200-9, 2015 Feb.
Article in En | MEDLINE | ID: mdl-25366275
ABSTRACT
The mechanistic target of rapamycin complex 1 (TORC1) senses nutrient availability to regulate eukaryotic anabolic metabolism. In response to limiting concentrations of amino acids, TORC1 kinase activity is inhibited through the GATOR-1 complex. Mutations in DEPDC5, that encodes one of the components of the GATOR-1 complex, have recently been associated with different forms of focal epilepsy. Here, we investigate the effects of 10 DEPDC5 variants identified in individuals with focal epilepsy and two DEPDC5 variants identified in serous ovarian tumors, on TORC1 signaling and GATOR-1 complex formation. According to our functional assessment, three variants clearly disrupted the DEPDC5-dependent inhibition of TORC1. We did not obtain functional evidence to support pathogenicity in the remaining cases. The observed functional differences between the DEPDC5 variants might underlie some of the clinical differences observed in the individuals carrying the different variants.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Hum Mutat Journal subject: GENETICA MEDICA Year: 2015 Type: Article Affiliation country: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Hum Mutat Journal subject: GENETICA MEDICA Year: 2015 Type: Article Affiliation country: Netherlands