The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep‐phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian‐relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires: the Pittsburgh Sleep Quality Index and the Morningness‐Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2‐related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.

中文翻译：

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PER2昼夜节律基因突变的自闭症谱系障碍患者的睡眠表型

在每基因功能的家庭大脑中的主要昼夜节律的维护。PER2 的突变与家族性晚期睡眠期综合征 1 (FASPS1) 相关，最近在延迟睡眠期综合征和特发性睡眠过多症中被提出。在自闭症谱系障碍 (ASD) 和没有报告睡眠障碍的个体中检测到PER2变异，表明昼夜节律相关基因在 ASD 的病理生理学中发挥作用。目前尚不清楚这些人是否可能除了 ASD 之外还患有未确诊的昼夜节律睡眠障碍。MSSNG 数据库用于筛选 5,102 名 ASD 个体的全基因组测序数据，以确定 PER2 中的假定突变. 邀请确定的家庭完成睡眠表型分析，包括结构化访谈和两个标准化睡眠问卷：匹兹堡睡眠质量指数和早晚问卷。从 5,102 名 ASD 患者中，确定了两个无意义、一个移码和一个从头错义PER2变体 (0.08%)。在这四人中，没有人被诊断出睡眠障碍。三人报告有睡眠障碍史或持续睡眠障碍，其中一人有高度提示 FASPS1 的症状（没有 ASD 的突变携带者父亲也是如此）。具有错义变异的个体没有报告睡眠问题。这些人的 ASD 和认知特征的严重程度和症状各不相同。结果支持PER2的可能作用与昼夜节律紊乱有关的整体睡眠失调，有时是 FASPS1。睡眠失调与 ASD 病理生理学之间的关系需要进一步探索。