B K Bulduk, J Tortajada, L Torres-Egurrola, A Valiente-Pallejà, R Martínez-Leal, E Vilella, H Torrell, G Muntané, L Martorell
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The aim of this study was to investigate the prevalence of large-scale mtDNA rearrangements in ID and ID with comorbid ASD (ID-ASD).</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":16163,"journal":{"name":"Journal of Intellectual Disability Research","volume":" ","pages":"e13197"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.\",\"authors\":\"B K Bulduk, J Tortajada, L Torres-Egurrola, A Valiente-Pallejà, R Martínez-Leal, E Vilella, H Torrell, G Muntané, L Martorell\",\"doi\":\"10.1111/jir.13197\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>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. 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引用次数: 0
摘要
背景:线粒体 DNA(mtDNA)重排是线粒体疾病和老龄化的公认因素,但人们对线粒体 DNA 重排参与神经发育疾病,尤其是智障(ID)和自闭症谱系障碍(ASD)的情况仍知之甚少。以前的研究曾报道过智力障碍和自闭症谱系障碍患者的线粒体功能障碍。本研究旨在调查线粒体DNA大规模重排在ID和ID合并自闭症谱系障碍(ID-ASD)患者中的发生率:我们使用mtDNA靶向新一代测序技术和MitoSAlt高通量计算管道,对来自加泰罗尼亚的76名ID患者(平均年龄52.5岁,37%为女性)、59名ID-ASD患者(平均年龄41.3岁,46%为女性)和32名健康对照者(平均年龄42.4岁,47%为女性)的外周血样本进行了检测:研究发现,ID 患者中 mtDNA 重排的频率很高,10/76(13.2%)人受到影响。然而,在ID-ASD患者和HC患者中,这一比例分别为1/59(1.7%)和1/32(3.1%),明显较低。在mtDNA重排中,有6个被鉴定为缺失(中位数大小为6937 bp,中位数异质性水平为2.3%),6个被鉴定为重复(中位数大小为10 455 bp,中位数异质性水平为1.9%)。其中一个重复序列,即 MT-ATP6 m.8765-8793dup (29 bp),出现在 4 个 ID 患者中,中位异源性水平为 3.9%:我们的研究结果表明,与 HC 相比,mtDNA 重排在 ID 患者中很常见,但在 ID-ASD 患者中并不常见。此外,MitoSAlt 在检测 mtDNA 重排方面表现出极高的灵敏度和准确性,即使血液样本中的异质性水平很低。虽然ID中mtDNA重排的高频率值得注意,但这些重排的作用目前尚不清楚,需要进一步的数据来证实,特别是在有丝分裂后组织中和通过年龄匹配的对照研究。
High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
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.
期刊介绍:
The Journal of Intellectual Disability Research is devoted exclusively to the scientific study of intellectual disability and publishes papers reporting original observations in this field. The subject matter is broad and includes, but is not restricted to, findings from biological, educational, genetic, medical, psychiatric, psychological and sociological studies, and ethical, philosophical, and legal contributions that increase knowledge on the treatment and prevention of intellectual disability and of associated impairments and disabilities, and/or inform public policy and practice. Expert reviews on themes in which recent research has produced notable advances will be included. Such reviews will normally be by invitation.