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端粒长度与家族性自闭症谱系障碍:与认知和感官症状的关系。

Telomere Length and Autism Spectrum Disorder Within the Family: Relationships With Cognition and Sensory Symptoms.

机构信息

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.

Southwest Autism Research and Resource Center, Phoenix, Arizona, USA.

出版信息

Autism Res. 2020 Jul;13(7):1094-1101. doi: 10.1002/aur.2307. Epub 2020 Apr 23.

Abstract

Telomeres are repetitive noncoding deoxynucleotide sequences that cap chromosomes to protect DNA. Telomere length (TL) is affected by both genetic and environmental factors, and shortening of telomeres is associated with multiple neuropsychiatric disorders, early life stress, and age-related cognitive dysfunction. Two previous studies associated shorter TL with autism spectrum disorder (ASD). We aimed to replicate this finding, describe TL in unaffected siblings, and explore novel relationships with symptoms and cognitive function in families with ASD. Participants were 212 male children and adolescents ages 1-17 years (86 with ASD, 57 unaffected siblings, and 69 typically developing [TD]) and 64 parents. TL was measured from blood leukocytes with quantitative real-time polymerase chain reaction and results are expressed by relative ratios with a single copy gene. We replicated that children and adolescents with ASD have shorter TL, compared to TD, and show that unaffected siblings have TL in between those of TD and ASD. We present novel associations between TL and sensory symptoms in ASD. Finally, we demonstrate cognitive functions, but not autistic traits, are related to TL in parents of children with ASD. Cognitive function and TL were not related in children and adolescents. As the third replication, our results elicit confidence in the finding that ASD is associated with shorter TL. Our novel sensory investigation suggests that shortened TL may be a biological mechanism of sensory symptoms in ASD. Furthermore, results highlight the need to better understand relationships between cognition, aging, and TL in families with ASD. Autism Res 2020, 13: 1094-1101. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Telomeres cap chromosomes to protect DNA. They progressively shorten as people age and are related to health outcomes. We replicated previous findings that children and adolescents with autism spectrum disorder (ASD) have shorter telomeres, compared to typically developing (TD), and show that unaffected siblings have telomere length (TL) in between those of TD and ASD. We find shortened TL is related to more severe sensory symptoms. This may mean families with ASD, especially those with elevated sensory symptoms, are at risk for worse age-related health outcomes.

摘要

端粒是重复的非编码脱氧核苷酸序列,可用于保护染色体 DNA。端粒长度(TL)受遗传和环境因素的影响,端粒缩短与多种神经精神疾病、生命早期压力和与年龄相关的认知功能障碍有关。先前有两项研究表明,TL 较短与自闭症谱系障碍(ASD)有关。我们旨在复制这一发现,描述未受影响的兄弟姐妹的 TL,并探索 ASD 家庭中与症状和认知功能的新关系。参与者为 212 名 1-17 岁的男性儿童和青少年(86 名患有 ASD、57 名未受影响的兄弟姐妹和 69 名典型发育 [TD])和 64 名父母。使用实时定量聚合酶链反应从血液白细胞中测量 TL,并以与单拷贝基因的相对比率表示结果。我们复制了 ASD 儿童和青少年的 TL 短于 TD,并且表明未受影响的兄弟姐妹的 TL 介于 TD 和 ASD 之间。我们提出了 TL 与 ASD 中感官症状之间的新关联。最后,我们证明了认知功能,但不是自闭症特征,与 ASD 儿童的父母的 TL 有关。儿童和青少年的认知功能和 TL 没有关系。作为第三次复制,我们的结果使人们有信心相信 ASD 与较短的 TL 有关。我们新的感官研究表明,TL 缩短可能是 ASD 中感官症状的生物学机制。此外,结果强调了需要更好地理解 ASD 家庭中认知、衰老和 TL 之间的关系。自闭症研究 2020,13:1094-1101。© 2020 自闭症国际研究协会,威利在线期刊,公司

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