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Article: Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome
Title | Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome |
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Authors | |
Issue Date | 2012 |
Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
Citation | Plos One, 2012, v. 7 n. 7 How to Cite? |
Abstract | Background: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. Objective: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. Methods: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. Results: Eighteen patients (9 males, 9 females) were diagnosed to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including truncating (7), splice site (2) and missense mutations (6). The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05). During the progression of disease, 73% (11/15) had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15) had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. Conclusion: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense variant were identified in a patient with Dravet syndrome. © 2012 Kwong et al. |
Persistent Identifier | http://hdl.handle.net/10722/170469 |
ISSN | 2023 Impact Factor: 2.9 2023 SCImago Journal Rankings: 0.839 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Kwong, AKY | en_US |
dc.contributor.author | Fung, CW | en_US |
dc.contributor.author | Chan, SY | en_US |
dc.contributor.author | Wong, VCN | en_US |
dc.date.accessioned | 2012-10-30T06:09:13Z | - |
dc.date.available | 2012-10-30T06:09:13Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | Plos One, 2012, v. 7 n. 7 | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/170469 | - |
dc.description.abstract | Background: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. Objective: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. Methods: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. Results: Eighteen patients (9 males, 9 females) were diagnosed to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including truncating (7), splice site (2) and missense mutations (6). The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05). During the progression of disease, 73% (11/15) had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15) had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. Conclusion: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense variant were identified in a patient with Dravet syndrome. © 2012 Kwong et al. | en_US |
dc.language | eng | en_US |
dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | en_US |
dc.relation.ispartof | PLoS ONE | en_US |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome | en_US |
dc.type | Article | en_US |
dc.identifier.email | Wong, VCN:vcnwong@hku.hk | en_US |
dc.identifier.authority | Wong, VCN=rp00334 | en_US |
dc.description.nature | published_or_final_version | en_US |
dc.identifier.doi | 10.1371/journal.pone.0041802 | en_US |
dc.identifier.pmid | 22848613 | - |
dc.identifier.scopus | eid_2-s2.0-84864366181 | en_US |
dc.identifier.hkuros | 214779 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-84864366181&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 7 | en_US |
dc.identifier.issue | 7 | en_US |
dc.identifier.eissn | 1932-6203 | - |
dc.identifier.isi | WOS:000306806600123 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Kwong, AKY=55322155900 | en_US |
dc.identifier.scopusauthorid | Fung, CW=55223837700 | en_US |
dc.identifier.scopusauthorid | Chan, SY=55322466500 | en_US |
dc.identifier.scopusauthorid | Wong, VCN=7202525632 | en_US |
dc.identifier.issnl | 1932-6203 | - |