Butler Merlin G, Nelson Tommy A, Driscoll Daniel J, Manzardo Ann M
Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas.
Department of Pediatrics and Center for Epigenetics, University of Florida Medical Center, Gainesville, Florida.
Am J Med Genet A. 2015 Aug;167A(8):1773-8. doi: 10.1002/ajmg.a.37103. Epub 2015 Apr 5.
Prader-Willi syndrome (PWS) is an obesity-related genetic condition, most commonly due to a paternal deletion of the chromosome 15q11-q13 region. PWS is characterized by growth hormone deficiency, infantile hypotonia and feeding problems, hypogenitalism/hypogonadism, increased pain threshold and thermal instability, decreased gastric motility, and hyperphagia in childhood leading to severe obesity. Neuro-endocrine peptides are known to influence gastric function and pain sensation which led us to measure a specific peptide that may be involved [i.e., neurotensin (NT)] in PWS and compared with unrelated control siblings. Overnight fasting plasma NT levels were obtained from 23 children with confirmed PWS (age: 8.2 ± 2.0 years; range: 5-11 years) and 18 unaffected, unrelated siblings (age: 8.2 ± 2.3 years; range: 5-11 years) and measured using Multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Plasma NT levels were natural log-transformed and analyzed by ANOVA with adjustments for age, gender, and body mass index (BMI). No difference was found in plasma NT levels for gender, age or BMI or significant correlations seen with age or BMI. Higher plasma NT levels (P < 0.001) were seen in PWS children (mean of 626 ± 238 pg/ml) compared with unaffected, unrelated siblings (mean of 371 ± 236 pg/ml). Plasma levels were also higher in children with maternal disomy 15 (736 ± 182 pg/ml) compared with those having the deletion subtype (548 ± 247 pg/ml, P < 0.04). Although no measures for pain threshold, thermal instability or gastric motility were performed in our study participants, higher plasma NT levels were found in PWS children.
普拉德-威利综合征(PWS)是一种与肥胖相关的遗传性疾病,最常见的原因是父源15号染色体q11-q13区域的缺失。PWS的特征包括生长激素缺乏、婴儿期肌张力减退和喂养问题、生殖器官发育不全/性腺功能减退、痛阈升高和体温不稳定、胃动力下降,以及儿童期食欲亢进导致严重肥胖。已知神经内分泌肽会影响胃功能和痛觉,这促使我们测量一种可能与PWS有关的特定肽[即神经降压素(NT)],并与无关的对照兄弟姐妹进行比较。从23名确诊为PWS的儿童(年龄:8.2±2.0岁;范围:5-11岁)和18名未受影响的无关兄弟姐妹(年龄:8.2±2.3岁;范围:5-11岁)中获取过夜禁食血浆NT水平,并使用基于Luminex磁珠平台的多重夹心免疫测定法进行测量。血浆NT水平进行自然对数转换,并通过方差分析进行分析,同时对年龄、性别和体重指数(BMI)进行调整。在性别、年龄或BMI方面,血浆NT水平没有差异,也未发现与年龄或BMI有显著相关性。与未受影响的无关兄弟姐妹(平均371±236 pg/ml)相比,PWS儿童的血浆NT水平更高(P<0.001)(平均626±238 pg/ml)。与缺失亚型的儿童(548±247 pg/ml,P<0.04)相比,母源15号染色体单亲二倍体的儿童血浆水平也更高(736±182 pg/ml)。尽管我们的研究参与者未进行痛阈、体温不稳定或胃动力的测量,但在PWS儿童中发现了较高的血浆NT水平。