Noonan综合征患儿PTPN11基因突变的临床及遗传分析  

PTPN11 gene mutation mediated Noonan syndrome in children with idiopathic short stature

作　　者：赵倩倩 张梅[1] 李艳英[1] 寇爽 邵倩[1] 班博[1] Zhao Qianqian;Zhang Mei;Li Yanying;Kou Shuang;Shao Qian;Ban Bo(Department of Endocrinology,Genetics and Metabolism,Affiliated Hospital of Jining Medical University,Jining 272029,China;School of Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]济宁医学院附属医院内分泌遗传代谢科,272029 [2]青岛大学医学部,266071

出　　处：《中华内分泌代谢杂志》2022年第9期775-780,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：山东省自然科学基金(ZR2014HP058)。

摘　　要：目的应用全外显子测序的方法分析特发性身材矮小(ISS)儿童的遗传学病因,探讨Noonan综合征患儿PTPN11基因突变的临床特征,并评估应用重组人生长激素(rhGH)治疗的效应。方法收集232例ISS患儿外周血提取基因组DNA,应用全外显子测序进行基因组检测,根据美国医学遗传学和基因组学(ACMG)指南对基因变异进行分析,筛选出PTPN11基因致病患儿进行临床基线资料及rhGH治疗随访资料收集。结果在232例ISS患儿中有6例患儿携带PTPN11致病性基因变异(c.1507G>C、c.317A>G、c.923A>G、c.922A>G、c.236A>G、c.922A>G),诊断为Noonan综合征;另外结合本院既往诊断的3例Noonan综合征患儿(均为PTPN11基因c.1510A>G位点变异),分析其临床特征。9例Noonan综合征患儿中,男孩7例,女孩2例,平均年龄为10.2(4.5,14.7)岁,身高标准差积分为-3.06 SD(95%CI-2.29 SD~-3.94 SD)。其中4例患儿接受rhGH治疗,平均治疗时间为2.25(1.5,3.5)年,治疗后身高增长14.3(8.6,23.9)cm,身高标准差积分改善0.21 SD(95%CI 0.12 SD~0.27 SD)。结论Noonan综合征临床表型广泛,对于身材矮小,同时伴有心脏缺陷及隐睾的患儿应考虑其可能,PTPN11基因是其常见的致病基因,基因检测有助于Noonan综合征患儿的早期诊断、治疗及随访预后。Objective To analyze the genetic etiology of idiopathic short stature(ISS)children,and to investigate the clinical characteristics of Noonan syndrome caused by PTPN11 gene mutation,and the response to recombinant human growth hormone(rhGH)as well.Methods Genomic DNA was extracted from the peripheral blood of 232 ISS patients,and the genome was detected by whole exon sequencing.The gene variation was analyzed according to the guideline of American College of Medical Genetics and Genomics(ACMG),and clinical baseline data and follow-up data of rhGH treatment were collected from PTPN11 gene pathogenic patients.Results Among 232 ISS patients,6 were found to have PTPN11 pathogenic gene variants(c.1507G>C,c.317A>G,c.923A>G,c.922A>G,c.236A>G,c.922A>G),diagnosed as Noonan syndrome.Together with 3 cases of Noonan syndrome patients(all PTPN11 gene variation C.1510A>G)previously diagnosed in our hospital,the clinical characteristics of patients were analyzed.Among the 9 Noonan syndrome patients,7 were boys and 2 were girls.The average age was 10.2(4.5,14.7)years old,and their height standard deviation score was-3.06 SD(95%CI-2.29 SD--3.94 SD).Among them,4 patients received rhGH treatment with an average treatment duration of 2.25(1.5,3.5)years.After treatment,their height increased by 14.3(8.6,23.9)cm,and the change in height standard deviation score improved by 0.21 SD(95%CI 0.12 SD-0.27 SD).Conclusion Noonan syndrome has a wide range of clinical phenotypes.For children with short stature,heart defects and cryptorchidism,the possibility of Noonan syndrome should be considered.PTPN11 is the common pathogenic gene for Noonan syndrome,and genetic testing facilitates the early diagnosis,treatment,and follow-up prognosis of Noonan syndrome patients.

关 键 词：特发性身材矮小 PTPN11基因 NOONAN综合征 重组人生长激素 

分 类 号：R725.8[医药卫生—儿科]