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Article: Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome

TitleIdentification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome
Authors
Issue Date2012
PublisherPublic 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?
AbstractBackground: 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 Identifierhttp://hdl.handle.net/10722/170469
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKwong, AKYen_US
dc.contributor.authorFung, CWen_US
dc.contributor.authorChan, SYen_US
dc.contributor.authorWong, VCNen_US
dc.date.accessioned2012-10-30T06:09:13Z-
dc.date.available2012-10-30T06:09:13Z-
dc.date.issued2012en_US
dc.identifier.citationPlos One, 2012, v. 7 n. 7en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/170469-
dc.description.abstractBackground: 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.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_US
dc.relation.ispartofPLoS ONEen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIdentification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndromeen_US
dc.typeArticleen_US
dc.identifier.emailWong, VCN:vcnwong@hku.hken_US
dc.identifier.authorityWong, VCN=rp00334en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0041802en_US
dc.identifier.pmid22848613-
dc.identifier.scopuseid_2-s2.0-84864366181en_US
dc.identifier.hkuros214779-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84864366181&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume7en_US
dc.identifier.issue7en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000306806600123-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKwong, AKY=55322155900en_US
dc.identifier.scopusauthoridFung, CW=55223837700en_US
dc.identifier.scopusauthoridChan, SY=55322466500en_US
dc.identifier.scopusauthoridWong, VCN=7202525632en_US

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