View in EDS HTML Full Text PDF Full Text

Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.

Saved in:
Bibliographic Details
Title: Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.
Authors: Wang, Chao (AUTHOR), Zhai, JinXia (AUTHOR), Chen, YongJun (AUTHOR)
Source: Neurological Sciences. Nov2024, Vol. 45 Issue 11, p5481-5488. 8p.
Subjects: Missense mutation, Genetic profile, Autism spectrum disorders, Genetic variation, Potassium channels
Abstract: Background: KCNQ is a voltage-gated K + channel that controls neuronal excitability and is mutated in epilepsy and autism spectrum disorder (ASD). We focus on the KV7.2 voltage-gated potassium channel gene (KCNQ2), which is known for its association with developmental delay and various seizures (including self-limited benign familial neonatal epilepsy and epileptic encephalopathy). But the pathogenicity of many variants remains unproven, potentially leading to misinterpretation of their functional consequences. Methods: In this study, we studied a patient who visited Nanhua Hospital. Targeted next-generation sequencing and Sanger sequencing were used to identify the pathogenic variants. Meanwhile, computational models, including hydrogen bonding and docking analyses, suggest that variants cause functional impairment. In addition, functional validation was performed in the drosophila to further evaluate the missense variant in the KCNQ2 gene as the cause of this patient. Results: A new missense variant in the KCNQ2 gene was identified: NM_172107.4:c.1007C > A(p.ALa336Glu), which resulted in the change from alanine to glutamate at amino acid position 336 in the KCNQ2 gene. After computational modeling, including hydrogen bond analysis and docking analysis, it is indicated that the variants cause functional impairment. Furthermore, RNAi-mediated KCNQ knockout in flies led to the onset of epileptic behavior, lifespan and climbing capacity were affected, expression of the normal human KCNQ2 rescues the in flies RNAi-mediated KCNQ knockout behavioral abnormalities. Conclusion: Our findings expands the genetic profile of KCNQ2 and enhances the genotype – phenotype link. [ABSTRACT FROM AUTHOR]
Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
Text:
  Availability: 1
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 180235785
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Wang%2C+Chao%22">Wang, Chao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhai%2C+JinXia%22">Zhai, JinXia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+YongJun%22">Chen, YongJun</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Neurological+Sciences%22">Neurological Sciences</searchLink>. Nov2024, Vol. 45 Issue 11, p5481-5488. 8p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Missense+mutation%22">Missense mutation</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+profile%22">Genetic profile</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+spectrum+disorders%22">Autism spectrum disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+variation%22">Genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Potassium+channels%22">Potassium channels</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: KCNQ is a voltage-gated K + channel that controls neuronal excitability and is mutated in epilepsy and autism spectrum disorder (ASD). We focus on the KV7.2 voltage-gated potassium channel gene (KCNQ2), which is known for its association with developmental delay and various seizures (including self-limited benign familial neonatal epilepsy and epileptic encephalopathy). But the pathogenicity of many variants remains unproven, potentially leading to misinterpretation of their functional consequences. Methods: In this study, we studied a patient who visited Nanhua Hospital. Targeted next-generation sequencing and Sanger sequencing were used to identify the pathogenic variants. Meanwhile, computational models, including hydrogen bonding and docking analyses, suggest that variants cause functional impairment. In addition, functional validation was performed in the drosophila to further evaluate the missense variant in the KCNQ2 gene as the cause of this patient. Results: A new missense variant in the KCNQ2 gene was identified: NM_172107.4:c.1007C > A(p.ALa336Glu), which resulted in the change from alanine to glutamate at amino acid position 336 in the KCNQ2 gene. After computational modeling, including hydrogen bond analysis and docking analysis, it is indicated that the variants cause functional impairment. Furthermore, RNAi-mediated KCNQ knockout in flies led to the onset of epileptic behavior, lifespan and climbing capacity were affected, expression of the normal human KCNQ2 rescues the in flies RNAi-mediated KCNQ knockout behavioral abnormalities. Conclusion: Our findings expands the genetic profile of KCNQ2 and enhances the genotype – phenotype link. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=180235785
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s10072-024-07655-w
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 8
        StartPage: 5481
    Subjects:
      – SubjectFull: Missense mutation
        Type: general
      – SubjectFull: Genetic profile
        Type: general
      – SubjectFull: Autism spectrum disorders
        Type: general
      – SubjectFull: Genetic variation
        Type: general
      – SubjectFull: Potassium channels
        Type: general
    Titles:
      – TitleFull: Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Wang, Chao
      – PersonEntity:
          Name:
            NameFull: Zhai, JinXia
      – PersonEntity:
          Name:
            NameFull: Chen, YongJun
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 11
              Text: Nov2024
              Type: published
              Y: 2024
          Identifiers:
            – Type: issn-print
              Value: 15901874
          Numbering:
            – Type: volume
              Value: 45
            – Type: issue
              Value: 11
          Titles:
            – TitleFull: Neurological Sciences
              Type: main
ResultId 1