Hanish Alyson E, Han Joan C
1 Unit on Metabolism and Neuroendocrinology, Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
2 National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.
Biol Res Nurs. 2018 Mar;20(2):237-243. doi: 10.1177/1099800417753670. Epub 2018 Jan 17.
PAX6 haploinsufficiency ( +/-) can occur due to mutations involving only PAX6 in patients with isolated aniridia or as contiguous gene deletions in patients with Wilms tumor, aniridia, genitourinary anomalies, and range of developmental and intellectual disabilities syndrome. Given the role of PAX6 in pineal development and circadian regulation, adolescents with PAX6+/- may experience sleep-wake disturbances. The purpose of this observational study was to explore sleep-related phenotypes in adolescents with PAX6+/-.
This study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years) with previously published data on healthy adolescents ( n = 25, aged 10-18 years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire (CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b) Questionnaires and wore actigraphs for seven nights to record sleep patterns.
Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep disturbance scores were not statistically different between the groups ( ps > .15). Actigraph data for lights off to sleep-onset time were found to be significantly higher in subjects with PAX6+/- versus the healthy comparison group (adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7, 10.4], respectively, p = .04).
Both adolescents with PAX6+/- and the healthy comparison group on average slept less than 8 hr/night, and overall sleep deprivation in adolescents may have masked differences between groups. This study used rare genetic disorders with biological vulnerability to sleep problems as a genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in designing studies to manage sleep-related symptoms in adolescents.
孤立性无虹膜患者仅因涉及PAX6的突变可出现PAX6单倍剂量不足（+/-），或者在患有威尔姆斯瘤、无虹膜、泌尿生殖系统异常以及一系列发育和智力残疾综合征的患者中作为连续性基因缺失而出现。鉴于PAX6在松果体发育和昼夜节律调节中的作用，PAX6+/-的青少年可能会出现睡眠-觉醒障碍。这项观察性研究的目的是探索PAX6+/-青少年的睡眠相关表型。
本研究将9名PAX6+/-受试者（年龄10 - 19岁）的睡眠表型与之前发表的关于健康青少年（n = 25，年龄10 - 18岁）的数据进行了比较。受试者完成了克利夫兰青少年嗜睡问卷（CASQ）、患者报告结局测量信息系统（PROMIS）睡眠障碍问卷（第1.0版；8a）和PROMIS睡眠相关损害问卷（第1.0版；8b），并佩戴活动记录仪7晚以记录睡眠模式。
两组之间的CASQ总分、PROMIS睡眠相关损害得分和PROMIS睡眠障碍得分无统计学差异（p值>.15）。发现PAX6+/-受试者从熄灯到入睡时间的活动记录仪数据显著高于健康对照组（调整后均值[95%置信区间]：分别为20.1分钟[8.1, 49.8]和6.2分钟[3.7, 10.4]，p = .04）。
PAX6+/-青少年和健康对照组平均每晚睡眠时间均少于8小时，青少年总体睡眠剥夺可能掩盖了两组之间的差异。本研究使用对睡眠问题具有生物学易感性的罕见遗传疾病作为基因型-表型模型。了解睡眠相关表型将有助于设计研究来管理青少年的睡眠相关症状。
