儿童17α-羟化酶/17,20碳链裂解酶缺陷症6例临床及CYP17A1基因突变分析  

Clinical and CYP17A1 gene mutation analysis of 6 children with 17α-hydroxylase/17,20-lyase deficiency

作　　者：宋福英[1] 刘子勤[1] 刘颖[1] 高亢 刘易 李国红[1] 董倩[1] 陈晓波[1] Song Fuying;Liu Ziqin;Liu Ying;Gao Kang;Liu Yi;Li Guohong;Dong Qian;Chen Xiaobo(Department of Endocrinology,Children′s Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院内分泌科,北京100020

出　　处：《中华实用儿科临床杂志》2021年第8期609-612,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：首都卫生发展科研专项(首发2018-2-2101)。

摘　　要：目的分析17α-羟化酶/17,20碳链裂解酶缺陷症(17OHD)的临床及CYP17A1基因突变特征。方法收集2014年3月至2019年12月首都儿科研究所附属儿童医院内分泌科收治的6例17OHD患儿的临床资料、实验室检查结果、CYP17A1基因突变情况,统计同期所有先天性肾上腺皮质增生症(CAH)的类型及数量。总结17OHD的临床特征及发病比例。结果6例患儿来自5个家庭,年龄1岁6个月~15岁,其中46,XX 2例,46,XY 4例;社会性别均为女性。临床表现中高血压3例(50.0%),低血钾4例(66.7%),阴唇包块1例(16.7%)。46,XY者性腺发育为睾丸;46,XX者子宫卵巢发育不良。实验室检查:8 AM皮质醇降低,为0.62~5.93 mg/L;促皮质素(ACTH)升高5例,为84~271 ng/L,1例ACTH正常(58 ng/L)的患儿行ACTH激发试验后皮质醇峰值仅为1.75 mg/L;6例均孕酮升高而17羟孕酮低下;睾酮、雌二醇减低,黄体生成素(LH)、卵泡刺激素(FSH)升高。肾上腺CT均示轻度增生。在114例同期诊断CAH患儿中,17OHD占5.3%,发病率居第2位。CYP17A1基因突变分析显示2例患儿p.Y329fs(c.985_987delTACinsAA)纯合突变;2例同胞患儿为p.Y329fs及外显子1-7缺失的复合杂合突变;1例患儿为p.Y329fs及p.R416C(c.1246C>T)的复合杂合突变;1例患儿p.L465P(c.1394T>C)纯合突变。p.L465P(c.1394T>C)首次见于中国人群。结论在CAH中,17OHD并不少见,对于女性外观的儿童低钾血症、高血压及性腺功能低下者警惕17OHD存在。p.Y329fs为中国儿童17OHD热点突变;p.L465P(c.1394T>C)为中国人群新发突变,其丰富了中国人CYP17A1基因突变谱系。Objective To analyze the clinical features and CYP17A1 gene mutation of 17α-hydroxylase/17,20-lyase deficiency(17OHD).Methods The clinical data,laboratory examination and genetic results of 6 children with 17OHD in the Department of Endocrinology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from March 2014 to December 2019 were enrolled and analyzed retrospectively.Meanwhile,the clinical types of all congenital adrenocortical hyperplasia(CAH)patients were calculated and then the incidence of 17OHD was calculated.Results The 6 cases were from 5 families,and the age at diagnosis was ranged from 1 year and 6 months to 15 years old,in which 2 cases were 46,XX and 4 cases were 46,XY.Their gender were all female.Three cases presented with hypertension(50.0%),4 cases with hypokalemia(66.7%),and 1 case with labia mass(16.7%).The gonad developed into a testis in patients with 46,XY,and patients with 46,XX had ovarian hypoplasia.The laboratory tests revealed an decrease in the cortisol at 8 AM in all cases,ranging from 0.62 to 5.93 mg/L.Five cases displayed an increase in adrenocorticotropic hormone(ACTH)in the range of 84-271 ng/L,and 1 patient with normal ACTH(58 ng/L)had a peak cortisol of 1.75 mg/L after the ACTH challenge test.Elevated progesterone was detected in 6 patients with a normal 17 hydroxyprogesterone level.Further results proved low levels of testosterone and estradiol,and high levels of luteinizing hormone(LH),and follicle stimulating hormone(FSH).CT scan showed mild adrenal hyperplasia in all cases.Among 114 CAH patients during the same period,the incidence of 17OHD came second at 5.3%.The CYP17A1 gene mutation results indicated that 2 unrelated patients were homozygous mutation for p.Y329fs(c.985_987delTACinsAA),2 siblings were compound heterozygous mutations for p.Y329fs and exon 1-7 deletion,1 patient was compound heterozygous mutations of p.Y329fs and p.R416C(c.1246C>T),and 1 patient was homozygous mutations for p.L465P(c.1394T>C),which was first reported in China.Conclusions 1

关 键 词：低钾血症 高血压 性腺功能低下 先天性肾上腺皮质增生症 17α-羟化酶/17 20碳链裂解酶缺陷症 CYP17A1基因 

分 类 号：R725.8[医药卫生—儿科]