Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disorders
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) trans...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00054/full |
| _version_ | 1811235695039086592 |
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| author | Mette eGilling Mette eGilling Hanne Borger Rasmussen Kirstine eCalloe Ana Filipa Sequeira Ana Filipa Sequeira Marta eBaretto Marta eBaretto Guiomar eOliveira Joana eAlmeida Marlene Briciet Lauritsen Reinhard eUllmann Susanne Eriksen Boonen Karen eBrøndum-Nielsen Vera M Kalscheuer Zeynep eTümer Zeynep eTümer Astrid M. Vicente Astrid M. Vicente Nicole eSchmitt Niels eTommerup |
| author_facet | Mette eGilling Mette eGilling Hanne Borger Rasmussen Kirstine eCalloe Ana Filipa Sequeira Ana Filipa Sequeira Marta eBaretto Marta eBaretto Guiomar eOliveira Joana eAlmeida Marlene Briciet Lauritsen Reinhard eUllmann Susanne Eriksen Boonen Karen eBrøndum-Nielsen Vera M Kalscheuer Zeynep eTümer Zeynep eTümer Astrid M. Vicente Astrid M. Vicente Nicole eSchmitt Niels eTommerup |
| author_sort | Mette eGilling |
| collection | DOAJ |
| 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 (ASD), epilepsy and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders. |
| first_indexed | 2024-04-12T11:56:23Z |
| format | Article |
| id | doaj.art-de1d7644a4a9429f891018223b1a6627 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T11:56:23Z |
| publishDate | 2013-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-de1d7644a4a9429f891018223b1a66272022-12-22T03:33:59ZengFrontiers Media S.A.Frontiers in Genetics1664-80212013-04-01410.3389/fgene.2013.0005441436Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disordersMette eGilling0Mette eGilling1Hanne Borger Rasmussen2Kirstine eCalloe3Ana Filipa Sequeira4Ana Filipa Sequeira5Marta eBaretto6Marta eBaretto7Guiomar eOliveira8Joana eAlmeida9Marlene Briciet Lauritsen10Reinhard eUllmann11Susanne Eriksen Boonen12Karen eBrøndum-Nielsen13Vera M Kalscheuer14Zeynep eTümer15Zeynep eTümer16Astrid M. Vicente17Astrid M. Vicente18Nicole eSchmitt19Niels eTommerup20University of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenInstituto Gulbenkian de CiênciaInstituto Nacional de Saúde Dr Ricardo JorgeInstituto Gulbenkian de CiênciaInstituto Nacional de Saúde Dr Ricardo JorgeFaculty of Medicine, University of CoimbraHospital Pediátrico de CoimbraAarhus University HospitalMax-Planck Institute for Molecular GeneticsCopenhagen University Hospital, RigshospitaletCopenhagen University Hospital, RigshospitaletMax-Planck Institute for Molecular GeneticsUniversity of CopenhagenCopenhagen University Hospital, RigshospitaletInstituto Gulbenkian de CiênciaInstituto Nacional de Saúde Dr Ricardo JorgeUniversity of CopenhagenUniversity of CopenhagenHeterozygous 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 (ASD), epilepsy and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00054/fullautismSNPtranslocationKCNQ3KCNQ5KV7.3 |
| spellingShingle | Mette eGilling Mette eGilling Hanne Borger Rasmussen Kirstine eCalloe Ana Filipa Sequeira Ana Filipa Sequeira Marta eBaretto Marta eBaretto Guiomar eOliveira Joana eAlmeida Marlene Briciet Lauritsen Reinhard eUllmann Susanne Eriksen Boonen Karen eBrøndum-Nielsen Vera M Kalscheuer Zeynep eTümer Zeynep eTümer Astrid M. Vicente Astrid M. Vicente Nicole eSchmitt Niels eTommerup Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disorders Frontiers in Genetics autism SNP translocation KCNQ3 KCNQ5 KV7.3 |
| title | 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_short | 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 |
| topic | autism SNP translocation KCNQ3 KCNQ5 KV7.3 |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00054/full |
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