View in EDS HTML Full Text PDF Full Text

High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.

Saved in:
Bibliographic Details
Title: High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
Authors: Bulduk, B. K., Tortajada, J., Torres‐Egurrola, L., Valiente‐Pallejà, A., Martínez‐Leal, R., Vilella, E., Torrell, H., Muntané, G., Martorell, L.
Source: Journal of Intellectual Disability Research. Feb2025, Vol. 69 Issue 2, p137-152. 16p.
Subjects: Blood testing, High throughput screening (Drug development), Statistical significance, Research funding, Autism, Gene rearrangement, Disease prevalence, Case-control method, Asperger's syndrome, Mitochondrial pathology, Mitochondrial DNA, Sequence analysis
Abstract: Background: Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large‐scale mtDNA rearrangements in ID and ID with comorbid ASD (ID‐ASD). Method: We used mtDNA‐targeted next‐generation sequencing and the MitoSAlt high‐throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5 years, 37% female), 59 patients with ID‐ASD (mean age 41.3 years, 46% female) and 32 healthy controls (mean age 42.4 years, 47% female) from Catalonia. Results: The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID‐ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937 bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455 bp and median heteroplasmy level 1.9%). One of the duplications, MT‐ATP6 m.8765‐8793dup (29 bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%. Conclusions: Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID‐ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post‐mitotic tissues and through age‐matched control studies. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Intellectual Disability Research is the property of Wiley-Blackwell 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: 184015106
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Bulduk%2C+B%2E+K%2E%22">Bulduk, B. K.</searchLink><br /><searchLink fieldCode="AR" term="%22Tortajada%2C+J%2E%22">Tortajada, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Torres‐Egurrola%2C+L%2E%22">Torres‐Egurrola, L.</searchLink><br /><searchLink fieldCode="AR" term="%22Valiente‐Pallejà%2C+A%2E%22">Valiente‐Pallejà, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Martínez‐Leal%2C+R%2E%22">Martínez‐Leal, R.</searchLink><br /><searchLink fieldCode="AR" term="%22Vilella%2C+E%2E%22">Vilella, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Torrell%2C+H%2E%22">Torrell, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Muntané%2C+G%2E%22">Muntané, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Martorell%2C+L%2E%22">Martorell, L.</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Journal+of+Intellectual+Disability+Research%22">Journal of Intellectual Disability Research</searchLink>. Feb2025, Vol. 69 Issue 2, p137-152. 16p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Blood+testing%22">Blood testing</searchLink><br /><searchLink fieldCode="DE" term="%22High+throughput+screening+%28Drug+development%29%22">High throughput screening (Drug development)</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+significance%22">Statistical significance</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Autism%22">Autism</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+rearrangement%22">Gene rearrangement</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+prevalence%22">Disease prevalence</searchLink><br /><searchLink fieldCode="DE" term="%22Case-control+method%22">Case-control method</searchLink><br /><searchLink fieldCode="DE" term="%22Asperger's+syndrome%22">Asperger's syndrome</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+pathology%22">Mitochondrial pathology</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+DNA%22">Mitochondrial DNA</searchLink><br /><searchLink fieldCode="DE" term="%22Sequence+analysis%22">Sequence analysis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large‐scale mtDNA rearrangements in ID and ID with comorbid ASD (ID‐ASD). Method: We used mtDNA‐targeted next‐generation sequencing and the MitoSAlt high‐throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5 years, 37% female), 59 patients with ID‐ASD (mean age 41.3 years, 46% female) and 32 healthy controls (mean age 42.4 years, 47% female) from Catalonia. Results: The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID‐ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937 bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455 bp and median heteroplasmy level 1.9%). One of the duplications, MT‐ATP6 m.8765‐8793dup (29 bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%. Conclusions: Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID‐ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post‐mitotic tissues and through age‐matched control studies. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Intellectual Disability Research is the property of Wiley-Blackwell 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=184015106
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/jir.13197
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 16
        StartPage: 137
    Subjects:
      – SubjectFull: Blood testing
        Type: general
      – SubjectFull: High throughput screening (Drug development)
        Type: general
      – SubjectFull: Statistical significance
        Type: general
      – SubjectFull: Research funding
        Type: general
      – SubjectFull: Autism
        Type: general
      – SubjectFull: Gene rearrangement
        Type: general
      – SubjectFull: Disease prevalence
        Type: general
      – SubjectFull: Case-control method
        Type: general
      – SubjectFull: Asperger's syndrome
        Type: general
      – SubjectFull: Mitochondrial pathology
        Type: general
      – SubjectFull: Mitochondrial DNA
        Type: general
      – SubjectFull: Sequence analysis
        Type: general
    Titles:
      – TitleFull: High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Bulduk, B. K.
      – PersonEntity:
          Name:
            NameFull: Tortajada, J.
      – PersonEntity:
          Name:
            NameFull: Torres‐Egurrola, L.
      – PersonEntity:
          Name:
            NameFull: Valiente‐Pallejà, A.
      – PersonEntity:
          Name:
            NameFull: Martínez‐Leal, R.
      – PersonEntity:
          Name:
            NameFull: Vilella, E.
      – PersonEntity:
          Name:
            NameFull: Torrell, H.
      – PersonEntity:
          Name:
            NameFull: Muntané, G.
      – PersonEntity:
          Name:
            NameFull: Martorell, L.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Text: Feb2025
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 09642633
          Numbering:
            – Type: volume
              Value: 69
            – Type: issue
              Value: 2
          Titles:
            – TitleFull: Journal of Intellectual Disability Research
              Type: main
ResultId 1