Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation. Issue 7 (5th June 2014)
- Record Type:
- Journal Article
- Title:
- Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation. Issue 7 (5th June 2014)
- Main Title:
- Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation
- Authors:
- Venkateswaran, Sunita
Myers, Ken A.
Smith, Amanda C.
Beaulieu, Chandree L.
Schwartzentruber, Jeremy A.
FORGE Canada Consortium
Majewski, Jacek
Bulman, Dennis
Boycott, Kym M.
Dyment, David A. - Abstract:
- <abstract abstract-type="main" id="epi12663-abs-0001"> <title>Summary</title> <p>We present a 4‐year‐old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole‐exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in <italic>GRIN2A</italic>, c.2449A&gt;G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. <italic>GRIN2A</italic> encodes a subunit of <italic>N</italic>‐methyl‐<sc>d</sc>‐aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10‐month period. Further prospective studies in additional patients with mutations in <italic>GRIN2A</italic> will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with <italic>GRIN2A</italic> mutations.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="uri"<abstract abstract-type="main" id="epi12663-abs-0001"> <title>Summary</title> <p>We present a 4‐year‐old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole‐exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in <italic>GRIN2A</italic>, c.2449A&gt;G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. <italic>GRIN2A</italic> encodes a subunit of <italic>N</italic>‐methyl‐<sc>d</sc>‐aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10‐month period. Further prospective studies in additional patients with mutations in <italic>GRIN2A</italic> will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with <italic>GRIN2A</italic> mutations.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="uri" xlink:href="http://onlinelibrary.wiley.com/doi/10.1111/epi.12663/suppinfo" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">here</ext-link>.</p> </abstract> … (more)
- Is Part Of:
- Epilepsia. Volume 55:Issue 7(2014:Jul.)
- Journal:
- Epilepsia
- Issue:
- Volume 55:Issue 7(2014:Jul.)
- Issue Display:
- Volume 55, Issue 7 (2014)
- Year:
- 2014
- Volume:
- 55
- Issue:
- 7
- Issue Sort Value:
- 2014-0055-0007-0000
- Page Start:
- e75
- Page End:
- e79
- Publication Date:
- 2014-06-05
- Subjects:
- Epilepsy -- Periodicals
616.853 - Journal URLs:
- http://www.blackwell-synergy.com/servlet/useragent?func=showIssues&code=epi ↗
http://onlinelibrary.wiley.com/ ↗ - DOI:
- 10.1111/epi.12663 ↗
- Languages:
- English
- ISSNs:
- 0013-9580
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 3793.700000
British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 4193.xml