儿童/青少年起病的特发性甲状旁腺功能减退症患者拷贝数变异研究  

Copy number variation in patients with childhood/adolescent-onset idiopathic hypoparathyroidism

作　　者：姜悦 宋桉 王亚冰 杨静 姜艳 李梅 夏维波 邢小平 聂敏 王鸥 JIANG Yue;SONG An;WANG Ya-bing;YANG Jing;JIANG Yan;LI Mei;XIA Wei-bo;XING Xiao-ping;NIE Min;WANG Ou(Department of Endocrinology,Key Laboratory of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Endocrinology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Clinical Laboratory,Huaihe Hospital of Henan University,Kaifeng,Henan 475000,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,国家卫生健康委员会内分泌重点实验室,北京100730 [2]首都医科大学附属北京友谊医院内分泌科,北京100050 [3]河南大学淮河医院检验科,河南开封475000

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2024年第6期553-563,共11页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(82070817);中国医学科学院医学与健康科技创新工程重大项目“内分泌肿瘤基础与临床研究”(2017-I2M-1-001)。

摘　　要：目的对本中心大样本儿童/青少年起病的特发性甲状旁腺功能减退症(idiopathic hypoparathyroidism,IHP)患者进行拷贝数变异(copy number variation,CNV)的筛查,描述其CNV的发生情况以及探索CNV与甲状旁腺功能减退症临床表型的相关性。方法纳入1975—2021年北京协和医院内分泌科随诊的儿童/青少年起病的IHP患者,按照性别比例匹配正常对照。回顾性收集患者的临床数据。通过低深度全基因组测序检测CNV(长度≥100 kb)携带情况。将IHP患者和正常对照的CNV发生率及负荷进行比较,并在IHP患者中比较CNV阳性组与阴性组、不同CNV负荷组间HP相关临床表型的差异。结果共有125例IHP患者进行了CNV分析,CNV阳性55例(44.0%),其中23例患者携带2个以上的CNV;20例正常对照中CNV阳性6例(30%),IHP患者和正常对照之间CNV的发生率及大小差异无统计学意义(均P>0.05)。CNV阳性和CNV阴性IHP患者间除儿童患者治疗后尿钙水平外,HP相关临床表型差异无统计学意义(均P>0.05);不同大小CNV组间也未发现HP相关临床表型的差异(均P>0.05)。在IHP患者中发现2例携带致病性或可能致病性CNV,但均未表现出CNV相关表型。结论本研究没有发现CNV(≥100 kb)与IHP或其临床表型显著相关,可能需要更大样本量、应用不同方法检测不同大小CNV在IHP发病机制中的可能作用。Objective To screen for copy number variation(CNV)in a large cohort of childhood/adolescent-onset idiopathic hypoparathyroidism(IHP)in a single center,and to explore the correlation between CNV and the clinical phenotype of HP.Methods The study included patients with childhood/adolescent-onset IHP who were followed at the Department of Endocrinology,Peking Union Medical College Hospital from 1975 to 2021.Normal controls were matched according to gender ratio.Clinical data were collected retrospectively.CNV(≥100 kb)were detected through low-depth whole-genome sequencing.The occurrence rate and burden of CNV in IHP patients were compared with those of controls.Differences in HP-related clinical phenotype were also compared among CNV-positive and CNV-negative groups,as well as among IHP patients with different CNV burdens.Results A total of 125 IHP patients underwent CNV analysis,among which 55 cases(44.0%)were CNV-positive,with 23 patients carrying more than two CNVs.Among the 20 normal controls,six(30%)were CNV-positive,with no significant differences in the occurrence rate and burden of CNV between IHP patients and controls(P>0.05).In addition,there were no significant difference in HP-related clinical phenotype between CNV-positive and CNV-negative groups(P>0.05),except for the post-treatment urine calcium levels in children;nor among patients with different burdens of CNV(P>0.05).One IHP patients carried pathogenic and another patient carried likely pathogenic CNVs,but no CNV-related phenotypes were observed.Conclusion A significant correlation between CNV(≥100 kb)and IHP or its clinical phenotype was not found in this study.Larger sample size and different methodologies might be required to explore the potential role of CNV of various sizes in the pathogenesis of IHP.

关 键 词：甲状旁腺功能减退症 拷贝数变异 低深度全基因组测序 临床表型 

分 类 号：R582.2[医药卫生—内分泌]