Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/1576 |
Resumo: | Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders. |
id |
RCAP_51e9b74085312604572a9d33bc5aef59 |
---|---|
oai_identifier_str |
oai:repositorio.insa.pt:10400.18/1576 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum DisordersAutismKCNQ3KCNQ5KV7.3KV7.5SNPTranslocationPerturbações do Desenvolvimento Infantil e Saúde MentalHeterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.Frontiers Research FoundationRepositório Científico do Instituto Nacional de SaúdeGilling, M.Rasmussen, H.B.Calloe, K.Sequeira, A.F.Barreto, M.Oliveira, G.Almeida, J.Lauritsen, M.B.Ullmann, R.Boonen, S.E.Brondum-Nielsen, K.Kalscheuer, V.M.Tümer, Z.Vicente, A.M.Schmitt, N.Tommerup, N.2013-04-26T15:00:53Z2013-04-162013-04-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/1576engFront Genet. 2013 Apr 16;4:54. doi: 10.3389/fgene.2013.000541664-8021doi: 10.3389/fgene.2013.00054info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:38:48Zoai:repositorio.insa.pt:10400.18/1576Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:36:40.110279Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
title |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
spellingShingle |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders Gilling, M. Autism KCNQ3 KCNQ5 KV7.3 KV7.5 SNP Translocation Perturbações do Desenvolvimento Infantil e Saúde Mental |
title_short |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
title_full |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
title_fullStr |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
title_full_unstemmed |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
title_sort |
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders |
author |
Gilling, M. |
author_facet |
Gilling, M. Rasmussen, H.B. Calloe, K. Sequeira, A.F. Barreto, M. Oliveira, G. Almeida, J. Lauritsen, M.B. Ullmann, R. Boonen, S.E. Brondum-Nielsen, K. Kalscheuer, V.M. Tümer, Z. Vicente, A.M. Schmitt, N. Tommerup, N. |
author_role |
author |
author2 |
Rasmussen, H.B. Calloe, K. Sequeira, A.F. Barreto, M. Oliveira, G. Almeida, J. Lauritsen, M.B. Ullmann, R. Boonen, S.E. Brondum-Nielsen, K. Kalscheuer, V.M. Tümer, Z. Vicente, A.M. Schmitt, N. Tommerup, N. |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Gilling, M. Rasmussen, H.B. Calloe, K. Sequeira, A.F. Barreto, M. Oliveira, G. Almeida, J. Lauritsen, M.B. Ullmann, R. Boonen, S.E. Brondum-Nielsen, K. Kalscheuer, V.M. Tümer, Z. Vicente, A.M. Schmitt, N. Tommerup, N. |
dc.subject.por.fl_str_mv |
Autism KCNQ3 KCNQ5 KV7.3 KV7.5 SNP Translocation Perturbações do Desenvolvimento Infantil e Saúde Mental |
topic |
Autism KCNQ3 KCNQ5 KV7.3 KV7.5 SNP Translocation Perturbações do Desenvolvimento Infantil e Saúde Mental |
description |
Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04-26T15:00:53Z 2013-04-16 2013-04-16T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/1576 |
url |
http://hdl.handle.net/10400.18/1576 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Front Genet. 2013 Apr 16;4:54. doi: 10.3389/fgene.2013.00054 1664-8021 doi: 10.3389/fgene.2013.00054 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799132099416948736 |