Author, as appears in the article.: Bulduk BK; Tortajada J; Torres-Egurrola L; Valiente-Pallejà A; Martínez-Leal R; Vilella E; Torrell H; Muntané G; Martorell L
Department: Medicina i Cirurgia
URV's Author/s: Bulduk, Bengisu Kevser / Martorell Bonet, Lourdes / Muntané Medina, Gerard / Tortajada Valero, Juan / Valiente Pallejà, Alba / Vilella Cuadrada, Elisabet
Keywords: Young adult Spectrum Mitosalt Mitosal Mitochondrial dna Middle aged Manifestations Male Intellectual disability Humans Heteroplasmy Gene rearrangement Female Dysfunction Duplication Dna, mitochondrial Disorders Disease Deletion Comorbidity Autism spectrum disorder Autism Aged Adult
Abstract: BackgroundMitochondrial 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).MethodWe 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.ResultsThe 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%.ConclusionsOur 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.
Thematic Areas: Rehabilitation Psychology Psychiatry and mental health Psychiatry Psicología Pedagogical & educational research Neurology (clinical) Neurology Medicina ii Medicina i Interdisciplinar Genetics & heredity Education, special Educació Educação física Clinical neurology Ciencias sociales Ciencias humanas Ciências biológicas ii Arts and humanities (miscellaneous)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: alba.valiente@urv.cat gerard.muntane@urv.cat lourdes.martorell@urv.cat elisabet.vilella@urv.cat juan.tortajada@estudiants.urv.cat bengisukevser.bulduk@estudiants.urv.cat
Author identifier: 0000-0003-4999-2197 0000-0002-1887-5919
Record's date: 2025-01-28
Paper version: info:eu-repo/semantics/publishedVersion
Paper original source: Journal Of Intellectual Disability Research. 69 (2): 137-152
APA: Bulduk BK; Tortajada J; Torres-Egurrola L; Valiente-Pallejà A; Martínez-Leal R; Vilella E; Torrell H; Muntané G; Martorell L (2025). High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability. Journal Of Intellectual Disability Research, 69(2), 137-152. DOI: 10.1111/jir.13197
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Entity: Universitat Rovira i Virgili
Journal publication year: 2025
Publication Type: Journal Publications
Repositori URV