儿童假性甲状旁腺功能减退症20例临床特征与GNAS基因缺陷分析  

Pseudohypoparathyroidism and GNAS gene defects: clinical evaluation and molecular analysis in 20 children

作　　者：许晓琴[1] 周雪莲[1] 陈雪峰[1] 袁金娜[1] 戴阳丽[1] 黄轲[1] 董关萍[1] 吴蔚[1] 傅君芬[1] Xu Xiaoqin;Zhou Xuelian;Chen Xuefeng;Yuan Jinna;Dai Yangli;Huang Ke;Dong Guanping;Wu Wei;Fu Junfen(Department of Endocrinology,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China)

机构地区：[1]浙江大学医学院附属儿童医院内分泌科,国家儿童健康与疾病临床医学研究中心,杭州310052

出　　处：《中华儿科杂志》2021年第3期206-211,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金(81471056);国家重点研发计划重大慢性非传染性疾病防控研究(2016YFC1305301);浙江省自然科学基金基础公益研究计划(LSZ19H070001);浙江省医药卫生重大科技计划(WKJ-ZJ-1804)。

摘　　要：目的:分析不同假性甲状旁腺功能减退症(PHP)亚型患儿的临床特征和分子遗传学改变,讨论不同PHP亚型之间临床表型与基因型的关联。方法:回顾性分析浙江大学医学院附属儿童医院2011年1月至2020年7月20例临床诊断PHP患儿的临床资料、实验室检查、基因检测结果及诊断分型。结果:20例患儿中男15例、女5例,其中甲状旁腺激素(PTH)抵抗有18例,具备Albright遗传性骨营养不良(AHO)表型的有13例。20例临床诊断PHP患儿均发现有基因异常,7例为GNAS基因变异,其中6例为移码变异,1例为错义变异;13例患儿为GNAS甲基化异常。共12例患儿同时具备PTH抵抗和AHO表型临床诊断PHP-Ⅰa型,其中7例为GNAS基因变异,5例为甲基化异常更正诊断为PHP-Ⅰb型。结论:以AHO或PTH抵抗作为典型表型进行PHP基因诊断,阳性率较高。PHP-Ⅰb型临床表型可与PHP-Ⅰa型相似,通过基因及甲基化检测方可明确诊断。PHP患儿早期亦可无PTH抵抗,分子遗传学检测可帮助明确诊断。Objective To analyze the patients′clinical and genetic characteristics with pseudohypoparathyroidism(PHP)and investigate the correlation between clinical phenotypes and genotypes.Methods Twenty PHP patients were ascertained at Children′s Hospital Zhejiang University School of Medicine from January 2011 to July 2020.Clinical manifestation,laboratory examination and gene test results were retrospectively analyzed.Results In these twenty patients,eighteen cases showed resistance to parathyroid hormone(PTH)and thirteen cases had Albright′s hereditary osteodystrophy(AHO)phenotype.Gene abnormalities were found in all the twenty PHP patients,which included seven patients with GNAS gene variations(six frameshifts and one missense)and thirteen patients with GNAS gene methylation defects.Moreover,twelve children with both PTH resistance and AHO phenotype were clinically diagnosed as PHP-Ⅰa,meanwhile,seven carried GNAS variations and five had methylation abnormalities with a correct diagnosis of PHP-Ⅰb.Conclusions Patients with AHO phenotype and PTH resistance may have a high genetic diagnosis rate.Because PHP-Ⅰb clinical phenotype may be similar to PHP-Ⅰa,early genetic detection is required for the differential diagnosis.In addition,children without PTH resistance should also be followed up regularly,which may help the early diagnosis.

关 键 词：假性甲状旁腺功能减退症 基因 甲基化 

分 类 号：R725.8[医药卫生—儿科]