Yang J, Wang Y B, Nie M, Jiang Y, Li M, Xia W B, Xing X P, Wang O
Key Laboratory of Endocrinology of National Health Commission, Union Translational Medicine Center,Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhonghua Nei Ke Za Zhi. 2022 Jan 1;61(1):66-71. doi: 10.3760/cma.j.cn112138-20210519-00356.
To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation. A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms. The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG). Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.
分析5例由GATA3基因突变引起的甲状旁腺功能减退症的临床特征及分子机制。从1975年至2021年北京协和医院收治的198例年龄≤18岁的甲状旁腺功能减退症患者中，共确诊5例儿童期起病的GATA3基因突变甲状旁腺功能减退症患者。回顾性收集并分析这5例患者的临床资料及生化指标。采用靶向二代测序（T-NGS）进行基因筛查，并进行生物信息学分析以探讨潜在机制。这5例甲状旁腺功能减退症患者的中位起病年龄为0.5（0.1，1.3）岁，从起病至确诊甲状旁腺功能减退症及甲状旁腺功能减退症-耳聋-肾发育不良综合征的时间分别为（7.0±5.2）年和（15.0±5.4）年。临床表现包括手足搐搦伴惊厥（5例）、基底节钙化（5例）、白内障（1例）、耳聋（4例）以及肾脏畸形或缺失（2例）。治疗前血钙及血甲状旁腺激素（PTH）水平分别为（1.65±0.31）mmol/L和（4.64±2.63）ng/L。这5例患者在GATA3基因中携带不同的杂合突变，分别导致无义突变、移码突变和剪接位点突变。根据Clin Var数据库及美国医学遗传学与基因组学学会（ACMG）的标准，这5例患者的所有GATA3基因突变均被分类为致病或可能致病。对于儿童期起病的甲状旁腺功能减退症患者应关注遗传性疾病。对于伴有听力丧失或肾脏发育异常 的甲状旁腺功能减退症患者，应考虑甲状旁腺功能减退症-耳聋-肾发育不良综合征的可能性。强烈建议进行GATA3基因筛查以确诊。
