Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities. Issue 4 (1st March 2014)
- Record Type:
- Journal Article
- Title:
- Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities. Issue 4 (1st March 2014)
- Main Title:
- Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities
- Authors:
- Baasch, Anna‐Lena
Hüning, Irina
Gilissen, Christian
Klepper, Joerg
Veltman, Joris A.
Gillessen‐Kaesbach, Gabriele
Hoischen, Alexander
Lohmann, Katja - Abstract:
- <abstract abstract-type="main" id="epi12554-abs-0001"> <title>Summary</title> <p>Epilepsy is a phenotypically and genetically highly heterogeneous disorder with &gt;200 genes linked to inherited forms of the disease. To identify the underlying genetic cause in a patient with intractable seizures, optic atrophy, severe intellectual disability (ID), brain abnormalities, and muscular hypotonia, we performed exome sequencing in a 5‐year‐old girl and her unaffected parents. In the patient, we detected a novel, de novo missense mutation in the <italic>SCN2A</italic> (c.5645G&gt;T; p.R1882L) gene encoding the α<sub>II</sub>‐subunit of the voltage‐gated sodium channel Na<sub>v</sub>1.2. A literature review revealed 33 different <italic>SCN2A</italic> mutations in 14 families with benign forms of epilepsy and in 21 cases with severe phenotypes. Although almost all benign mutations were inherited, the majority of severe mutations occurred de novo. Of interest, de novo <italic>SCN2A</italic> mutations have also been reported in five patients without seizures but with ID (n = 3) and/or autism (n = 3). In the present study, we successfully used exome sequencing to detect a de novo mutation in a genetically heterogeneous disorder with epilepsy and ID. Using this approach, we expand the phenotypic spectrum of <italic>SCN2A</italic> mutations. Our own and literature data indicate that <italic>SCN2A</italic>‐linked severe phenotypes are more likely to be caused by de novo mutations.</p> <p>A<abstract abstract-type="main" id="epi12554-abs-0001"> <title>Summary</title> <p>Epilepsy is a phenotypically and genetically highly heterogeneous disorder with &gt;200 genes linked to inherited forms of the disease. To identify the underlying genetic cause in a patient with intractable seizures, optic atrophy, severe intellectual disability (ID), brain abnormalities, and muscular hypotonia, we performed exome sequencing in a 5‐year‐old girl and her unaffected parents. In the patient, we detected a novel, de novo missense mutation in the <italic>SCN2A</italic> (c.5645G&gt;T; p.R1882L) gene encoding the α<sub>II</sub>‐subunit of the voltage‐gated sodium channel Na<sub>v</sub>1.2. A literature review revealed 33 different <italic>SCN2A</italic> mutations in 14 families with benign forms of epilepsy and in 21 cases with severe phenotypes. Although almost all benign mutations were inherited, the majority of severe mutations occurred de novo. Of interest, de novo <italic>SCN2A</italic> mutations have also been reported in five patients without seizures but with ID (n = 3) and/or autism (n = 3). In the present study, we successfully used exome sequencing to detect a de novo mutation in a genetically heterogeneous disorder with epilepsy and ID. Using this approach, we expand the phenotypic spectrum of <italic>SCN2A</italic> mutations. Our own and literature data indicate that <italic>SCN2A</italic>‐linked severe phenotypes are more likely to be caused by de novo mutations.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">here</ext-link>.</p> </abstract> … (more)
- Is Part Of:
- Epilepsia. Volume 55:Issue 4(2014:Apr.)
- Journal:
- Epilepsia
- Issue:
- Volume 55:Issue 4(2014:Apr.)
- Issue Display:
- Volume 55, Issue 4 (2014)
- Year:
- 2014
- Volume:
- 55
- Issue:
- 4
- Issue Sort Value:
- 2014-0055-0004-0000
- Page Start:
- e25
- Page End:
- e29
- Publication Date:
- 2014-03-01
- 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.12554 ↗
- 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:
- 3719.xml