假性甲状旁腺功能减退症家系GNAS基因突变位点及其功能分析  

An analysis of GNAS gene mutation site and its function in a pseudohypoparathyroidism family

作　　者：邱樊[1] 朱功民 吕园[1] 立彦[1] 瞿卫[1] QIU Fan;ZHU Gongmin;LYU Yuan(Department of Nuclear Medicine,Nanjing First Hospital,Nanjing Medical University,Nanjing 210006,CHINA)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)核医学科

出　　处：《江苏医药》2020年第1期43-46,F0003,共5页Jiangsu Medical Journal

摘　　要：目的探讨假性甲状旁腺功能减退症(PHP)家系GNAS基因突变位点及其在PHP发病中的作用。方法选取1个PHP家系为研究对象,检测甲状旁腺激素(PTH)、甲状腺激素、垂体激素及电解质等生化指标。甲状旁腺显像用于原发性甲状旁腺功能亢进的鉴别诊断,头颅CT及四肢X射线片用于检测骨骼无机盐代谢及骨骼发育是否异常,外显子测序及甲基化分析用于检测GNAS基因突变。生物信息学分析GNAS基因突变对Gsα蛋白的影响。结果先证者确诊为PHPⅠa。在所有PTH抵抗的女性成员中,发现了1个低频突变位点c.136G>A。仅在先证者中发现了1个错义突变c.502A>G(168Asn>Asp),该突变导致Gsα蛋白不稳定,可能与先证者的临床表现相关。结论 PHP患者诊断为PHPⅠa,该家系发现了2个突变位点c.136G>A和c.502A>G。c.136G>A与PTH抵抗相关,c.502A>G引起更显著的临床症状。Objective To investigate GNAS gene mutation site in a pseudohypoparathyroidism(PHP) family and its effects on the pathogenesis of PHP.Methods A PHP family was selected,and the biochemical tests including parathyroid hormone(PTH),thyroid hormone,hypophyseal hormone and electrolyte were detected.Parathyroid scintigraphy was used to diagnose primary hyperparathyroidism.Cranium CT and extremities radiograph were used to evaluate bone metabolism of inorganic salts and bone abnormality.Exome sequencing and methylation specific multiple ligation-dependent probe amplification were used to detect GNAS mutation.Bioinformatics was used to investigate the effect of GNAS gene mutation on Gsα protein.Results The proband was diagnosed as PHPⅠa.A low frequency mutation c.136 G>A was identified in all members of the femaly with PTH resistance.A novel mutation c.502 A>G(168 Asn>Asp) was identified only in the proband with most obviously clinical symptoms,which located in the highly conserved region of GNAS and may cause the instability of Gsα.Conclusion The PHP patient has been diagnosed as PHPⅠa,and c.136 G>A and c.502 A>G mutation sites are identified in this family.The c.136 G>A mutation is associated with PTH resistance,while c.502 A>G may lead to more obviously clinical manifestations.

关 键 词：假性甲状旁腺功能减退症 GNAS基因 Gsα蛋白 基因突变 

分 类 号：R582[医药卫生—内分泌]