4例Ib型假性甲状旁腺功能减退症的临床和遗传学特征  

Clinical and genetic characteristics for 4 patients with Type Ib pseudohypoparathyroidism

作　　者：王玉君 杨文君 金萍[1] 赵立玲[1] 何红晖[1] WANG Yujun;YANG Wenjun;JIN Ping;ZHAO Liling;HE Honghui(Department of Endocrinology,Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院内分泌科,长沙410013

出　　处：《中南大学学报（医学版）》2022年第10期1461-1466,共6页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81670730);湖南省自然科学基金(2021JJ31007);湖南省卫生健康委员会科研计划(202103061081)。

摘　　要：假性甲状旁腺功能减退症(pseudohypoparayhyroidism,PHP)是一种罕见的常染色体显性或隐性遗传疾病,临床上以低血钙、高血磷及靶器官对甲状旁腺激素抵抗为主要特征。中南大学湘雅三医院收治的4例Ib型PHP患者均存在低血钙、高血磷和甲状旁腺激素抵抗,其中2例患者有促甲状腺激素轻度升高和Albright遗传性骨营养不良症的轻微表现,1例患者合并低钾血症。4例患者全外显子组测序均未发现GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1)及低钾相关基因变异。多重连接探针扩增检测提示4例患者均存在GNAS基因上游甲基化差异表达区域的甲基化异常。PHP各亚型之间存在表型重叠,故对临床怀疑Ib型PHP患者进行GNAS甲基化检测有助于本病的诊断及治疗。Pseudohypoparayhyroidism(PHP)is a rare autosomal dominant or recessive genetic disorder characterized by low calcium,high phosphorus,and target organ resistance to parathyroid.The clinical characteristics and genetic features in 4 patients with Type Ib PHP in the Third Xiangya Hospital,Central South University,have been reviewed.All 4 patients had low calcium,high phosphorus,and parathyroid resistance.Among them,2 patients had slightly elevated thyroid stimulating hormone and mild features of Albright’s hereditary osteodystrophy,and one patient had hypokalemia.No guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1(GNAS)and gene variant associated with hypokalemia were identified using the whole exome sequencing.The results of the methylation-specific multiple ligation-dependent probe amplification showed that there were abnormal methylation of the upstream differentially methylated regions of GNAS in the 4 patients.There were phenotype overlap among the various subtypes of PHP.Detection of GNAS gene methylation in patients with clinical suspicion of Type Ib PHP is helpful for the diagnosis and treatment of PHP.

关 键 词：假性甲状旁腺功能减退症Ib型 GNAS基因 甲基化 多重连接探针扩增 

分 类 号：R582.2[医药卫生—内分泌]