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Conference Paper: Dravet syndrome - genetic analysis of SCN1A and PCDH19 mutations for 17 Chinese children

TitleDravet syndrome - genetic analysis of SCN1A and PCDH19 mutations for 17 Chinese children
Authors
KeywordsMedical sciences
Pediatrics medical sciences
Psychiatry and neurology
Issue Date2012
PublisherMac Keith Press. The Journal's web site is located at http://www.mackeith.co.uk/journal.html
Citation
The Joint 12th International Child Neurology Congress (ICNC 2012) and the 11th Asian and Oceanian Congress of Child Neurology, Brisbane, Australia, 27 May-1 June 2012. In Developmental Medicine and Child Neurology, 2012, v. 54 suppl. s4, p. 124, abstract B3-0014 How to Cite?
AbstractOBJECTIVE: In Dravet syndrome (DS), 80% of patients will have a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. A recent study demonstrated that 16%of SCN1A-negative patients had mutations in the protocadherin-19 (PCDH19) gene. The present study examines the genetic mutations in Chinese DS children and assesses the relationship between mutation and phenotype. DESIGN: Prospective cohort study. METHOD: DNA of 17 DS children seen at The University of Hong Kong was screened for SCN1A mutations using polymerase chain reaction and direct sequencing. SCN1Anegative female patients were then screened for PCDH19 mutation. RESULTS: For DS cases, 82% (14/17) had SCN1A mutations that included truncating mutations (6), splice site mutations (2) and missense mutations (6). These mutations affected Nav1.1 protein function on pathogenicity assessments including conservative, SIFT and Align-GVGD analyses. We found a relationship between the type of mutation and the degree of intellectual disability (P<0.05), with truncating/splice site mutations associated with moderate/severe mental retardation. At the onset of the disease, 79% (11/14) of DS patients with SCN1A mutations had features consistent with a diagnosis of autism spectrum disorder (ASD). Fifty-seven percent (8/14) had a history of vaccination-induced seizures. One of the two female SCN1A-negative patients had PCDH19 mutation. CONCLUSION: A high percentage of genetic mutations were identified in our Chinese cohort with DS. Pathogenicity assessments demonstrated that the mutations were linked to the phenotypes of DS. Our detection of a high frequency of ASD (79%) and vaccination-induced encephalopathy (57%) in those DS with SCN1A mutation suggests that patients with ASD with epilepsy or with vaccination-induced encephalopathy should be investigated for SCN1A mutations.
DescriptionThis journal suppl. is Special Issue: Abstracts of the 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology ... 2012
Concurrent Poster Sessions - Stream B: Epilepsy: B3-0014
Persistent Identifierhttp://hdl.handle.net/10722/153130
ISSN
2015 Impact Factor: 3.615
2015 SCImago Journal Rankings: 1.636

 

DC FieldValueLanguage
dc.contributor.authorWong, Ven_US
dc.contributor.authorKwong, A-
dc.contributor.authorFung, CW-
dc.date.accessioned2012-07-16T09:57:35Z-
dc.date.available2012-07-16T09:57:35Z-
dc.date.issued2012en_US
dc.identifier.citationThe Joint 12th International Child Neurology Congress (ICNC 2012) and the 11th Asian and Oceanian Congress of Child Neurology, Brisbane, Australia, 27 May-1 June 2012. In Developmental Medicine and Child Neurology, 2012, v. 54 suppl. s4, p. 124, abstract B3-0014en_US
dc.identifier.issn0012-1622-
dc.identifier.urihttp://hdl.handle.net/10722/153130-
dc.descriptionThis journal suppl. is Special Issue: Abstracts of the 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology ... 2012-
dc.descriptionConcurrent Poster Sessions - Stream B: Epilepsy: B3-0014-
dc.description.abstractOBJECTIVE: In Dravet syndrome (DS), 80% of patients will have a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. A recent study demonstrated that 16%of SCN1A-negative patients had mutations in the protocadherin-19 (PCDH19) gene. The present study examines the genetic mutations in Chinese DS children and assesses the relationship between mutation and phenotype. DESIGN: Prospective cohort study. METHOD: DNA of 17 DS children seen at The University of Hong Kong was screened for SCN1A mutations using polymerase chain reaction and direct sequencing. SCN1Anegative female patients were then screened for PCDH19 mutation. RESULTS: For DS cases, 82% (14/17) had SCN1A mutations that included truncating mutations (6), splice site mutations (2) and missense mutations (6). These mutations affected Nav1.1 protein function on pathogenicity assessments including conservative, SIFT and Align-GVGD analyses. We found a relationship between the type of mutation and the degree of intellectual disability (P<0.05), with truncating/splice site mutations associated with moderate/severe mental retardation. At the onset of the disease, 79% (11/14) of DS patients with SCN1A mutations had features consistent with a diagnosis of autism spectrum disorder (ASD). Fifty-seven percent (8/14) had a history of vaccination-induced seizures. One of the two female SCN1A-negative patients had PCDH19 mutation. CONCLUSION: A high percentage of genetic mutations were identified in our Chinese cohort with DS. Pathogenicity assessments demonstrated that the mutations were linked to the phenotypes of DS. Our detection of a high frequency of ASD (79%) and vaccination-induced encephalopathy (57%) in those DS with SCN1A mutation suggests that patients with ASD with epilepsy or with vaccination-induced encephalopathy should be investigated for SCN1A mutations.-
dc.languageengen_US
dc.publisherMac Keith Press. The Journal's web site is located at http://www.mackeith.co.uk/journal.html-
dc.relation.ispartofDevelopmental Medicine and Child Neurologyen_US
dc.subjectMedical sciences-
dc.subjectPediatrics medical sciences-
dc.subjectPsychiatry and neurology-
dc.titleDravet syndrome - genetic analysis of SCN1A and PCDH19 mutations for 17 Chinese childrenen_US
dc.typeConference_Paperen_US
dc.identifier.emailWong, V: vcnwong@hku.hken_US
dc.identifier.emailKwong, A: kkyanna@hku.hk-
dc.identifier.emailFung, CW: fcw1209m@hkucc.hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1469-8749.2012.04283.x-
dc.identifier.hkuros200484en_US
dc.identifier.hkuros200744-
dc.identifier.volume54-
dc.identifier.issuesuppl. s4-
dc.identifier.spage124-
dc.identifier.epage124-
dc.publisher.placeUnited Kingdom-
dc.customcontrol.immutablesml 130415-

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