不同基因型Prader-Willi综合征患者临床生化特征和治疗效果差异分析  

Analysis of differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome

作　　者：于冰青 贾淞蕊 高寅洁 茅江峰 王曦 聂敏 伍学焱 Yu Bingqing;Jia Songrui;Gao Yinjie;Mao Jiangfeng;Wang Xi;Nie Min;Wu Xueyan(Department of Endocrinology,Chinese Academy of Medical Sciences,Peking Union Medical College Hospital,Peking Union Medical College,NHC Key laboratory of Endocrinology,Beijing 100005,China;Department of Clinical Pharmacy,School of Pharmaceutical Science,Capital Medical University,Beijing 100069,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院内分泌科,卫生健康委员会内分泌重点实验室,北京100005 [2]首都医科大学药学院临床药学系,北京100069

出　　处：《中华医学杂志》2021年第35期2760-2765,共6页National Medical Journal of China

基　　金：国家自然科学基金(81771576)。

摘　　要：目的:分析不同基因型Prader-Willi综合征(PWS)患者临床生化特征和治疗效果的差异。方法:回顾性纳入2017年5月至2018年12月于北京协和医院内分泌科门诊就诊的35例PWS患者,其中男20例,女15例,年龄[M(Q_(1),Q_(3))][3.0(0.8,10.0)]岁。收集患者的临床和生化资料,并采集外周血标本。提取患者外周血白细胞DNA,用甲基化特异性多重连接探针扩增技术(MS-MLPA)检测患者基因缺失或甲基化异常,并据此分组(父源缺失组27例,甲基化异常组8例),分析两组患者生化检查结果及生长激素的治疗效果。结果:MS-MLPA技术检测示77%(27/35)的患者基因型为父源缺失型,23%(8/35)患者为甲基化异常。生化检查结果方面,父源缺失组患者尿酸(UA)水平高于甲基化异常组[(363±101)μmol/L比(259±74)μmol/L,P=0.019]。体重与尿酸水平之间存在线性关系,经体重校正后,父源缺失组与甲基化异常组患者尿酸水平差异无统计学意义(P=0.101)。两组患者均应用生长激素[剂量:每天(0.14±0.03)U/kg]治疗。父源缺失组患者随访(26.0±13.6)个月,身高由(99.0±31.5)cm[(-0.3±1.1)同年龄同性别儿童身高标准差(SDS)]增加至(107.5±27.0)cm[(0.7±0.9)SDS](P=0.037);甲基化异常组患者随访(25.8±11.6)个月,患者身高由(86.4±31.2)cm[(-0.7±1.8)SDS]增加至(95.6±26.5)cm[(0.0±1.6)SDS](P=0.557)。治疗前后父源缺失组和甲基化异常组患者体质指数差异无统计学意义[(22.0±7.1)kg/m^(2)比(22.4±6.8)kg/m^(2),P=0.890;(17.0±3.1)kg/m^(2)比(16.4±2.7)kg/m^(2),P=0.754]。结论:父源缺失和甲基化异常的PWS患者生化检查结果差异无统计学意义。PWS患者早期应用生长激素治疗可有效促进身高增长,控制体重增加。Objective To analyze the differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome(PWS).Methods A total of 35 patients with PWS,20 males and 15 females aged from 0.8 to 10.0 years with an average age of 3.0 years,were retrospectively included in this study.All of them were treated in the Department of Endocrinology of Peking Union Medical College Hospital from May 2017 to December 2018.The clinical material,biochemical data,and peripheral blood samples of the patients were collected.Genomic DNA was extracted from peripheral blood leukocytes of patients,and methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA)was used to detect gene deletion or abnormal methylation.According to the results of detection,35 patients were divided into two groups:paternal deletion group(n=27)and methylation abnormal group(n=8).The biochemical test results and the effect of growth hormone(GH)treatment of the two groups were analyzed.Results MS-MLPA showed that 77%(27/35)of the patients were confirmed paternal deletion and 23%(8/35)were abnormal methylation.In terms of biochemical test results,the plasma concentrations of uric acid(UA)in the paternal deletion group were higher than that in the abnormal methylation group[(363±101)μmol/L vs(259±74)μmol/L,P=0.019].There is a linear relationship between body weight and uric acid level.After adjustment for weight.,there was no significant difference in UA level between the two groups(P=0.101).Patients in both groups were treated with GH((0.14±0.03)U/kg,QD).In paternal deletion group,patients were followed up for(26.0±13.6)months,and their height increased from(99.0±31.5)cm[(-0.3±1.1)SDS]to(107.5±27.0)cm[(0.7±0.9)SDS](P=0.037).In the abnormal methylation group,patients were followed up for(25.8±11.6)months,and their height increased from(86.4±31.2)cm[(-0.7±1.8)SDS]to(95.6±26.5)cm[(0.0±1.6)SDS](P=0.557).There was no significant difference in body mass index(BMI)between pate

关 键 词：PRADER-WILLI综合征 MS-MLPA 父源缺失 甲基化异常 

分 类 号：R725.9[医药卫生—儿科]