High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability
Year: 2024
Type: article
Study design: Observational Study
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.
DOI: 10.1111/jir.13197
Authors: B. K. Bulduk, J. Tortajada, L. Torres‐Egurrola, A. Valiente‐Pallejà, R. Martínez‐Leal, E. Vilella, H. Torrell, G. Muntané, L. Martorell
Institutions: Institut Pere Mata, Institut de Recerca Biomèdica Catalunya Sud, Universitat Rovira i Virgili, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Centre for Omic Sciences, EURECAT Centre Tecnològic de Catalunya, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Institut de Biologia Evolutiva
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,730
Awards: G161125253, Estudio piloto aleatorizado y controlado a doble ciego sobre la eficacia de los nutracéuticos combinados con la actividad física como tratamiento complementario para el autismo y la esquizofrenia., G3518855215, Implicación del ADN mitocondrial en las psicosis tempranas: relación con el riesgo de enfermedad, estrés, rendimiento cognitivo, sintomatología clínica y síndrome metabólico., G4479234481, G6131083278
OpenAlex ID: W4404151341