Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China.
Clin Endocrinol (Oxf). 2018 Feb;88(2):285-294. doi: 10.1111/cen.13516. Epub 2017 Dec 14.
Pseudohypoparathyroidism (PHP) is caused by mutations and epimutations in the GNAS locus, and characterized by the possibility of resistance to multiple hormones and Albright's hereditary osteodystrophy. PHP can be classified into the forms 1A/C, sporadic 1B and familial 1B.
To obtain an overall view of the clinical and genetic characteristics of the Chinese PHP patient population.
From 2000 to 2016, 120 patients were recruited and studied using Sanger sequencing, methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) and combined bisulfite restriction analysis (COBRA). Of these patients, 104 had positive molecular alterations indicative of certain forms of PHP and were included in data analysis. Clinical and laboratory features were compared between PHP1A/C and PHP1B patients.
Ten PHP1A/C, 21 familial PHP1B and 73 sporadic PHP1B patients were identified. Four novel GNAS mutations were discovered in these patients, including c.1038+1G>T, c.530+2T>C, c.880_883delCAAG and c.311_312delAAG, insT. The most common symptoms in this series were recurrent tetany (89.4%) and epilepsy (47.1%). The prevalence of weight excess increased with age for PHP1B (10%-35%) and PHP1A/C (50%-75%). Intracranial calcification had a prevalence of 94.6% and correlated with seizures (r = .227, P = .029). Cataracts occurred in 56.2% PHP patients, and there was a trend towards longer disease duration in patients with cataracts (P = .051). Statistically significant differences (P < .05) were observed when comparing certain clinical characteristics between PHP1B and PHP1A/C patients, including age of onset (10 vs 7 year), short stature (21.3% vs 70%), rounded face (60.6% vs 100%), brachydactyly (25.5% vs 100%), ectopic ossification (1.1% vs 40%) and TSH resistance (44.6% vs 90%), respectively.
This study is the largest single-centre series of PHP patients and summarizes the clinical and genetic features of the Chinese PHP population. While there was substantial clinical overlap between PHP1A/C and PHP1B, differences in disease progression were observed.
假性甲状旁腺功能减退症（PHP）是由 GNAS 基因座的突变和表观突变引起的，其特征是对多种激素的抵抗和阿-罗二氏遗传性骨营养不良。PHP 可分为 1A/C 型、散发性 1B 型和家族性 1B 型。
获得中国 PHP 患者人群的临床和遗传特征的全貌。
2000 年至 2016 年，通过桑格测序、甲基化特异性多重连接依赖性探针扩增（MS-MLPA）和联合亚硫酸氢盐限制分析（COBRA），对 120 例患者进行了招募和研究。其中 104 例患者具有 PHP 特定形式的阳性分子改变，并纳入数据分析。比较 PHP1A/C 和 PHP1B 患者的临床和实验室特征。
确定了 10 例 PHP1A/C、21 例家族性 PHP1B 和 73 例散发性 PHP1B 患者。在这些患者中发现了 4 种新的 GNAS 突变，包括 c.1038+1G>T、c.530+2T>C、c.880_883delCAAG 和 c.311_312delAAG，insT。该系列中最常见的症状是复发性手足搐搦（89.4%）和癫痫（47.1%）。随着年龄的增长，PHP1B（10%-35%）和 PHP1A/C（50%-75%）患者的体重超重患病率增加。颅内钙化的患病率为 94.6%，与癫痫发作相关（r=0.227，P=0.029）。56.2%的 PHP 患者发生白内障，白内障患者的疾病持续时间呈延长趋势（P=0.051）。与 PHP1B 患者相比，PHP1A/C 患者的某些临床特征存在显著差异（P<.05），包括发病年龄（10 岁 vs 7 岁）、身材矮小（21.3% vs 70%）、圆脸（60.6% vs 100%）、短指（25.5% vs 100%）、异位骨化（1.1% vs 40%）和 TSH 抵抗（44.6% vs 90%）。
本研究是最大的单中心 PHP 患者系列研究，总结了中国 PHP 人群的临床和遗传特征。虽然 PHP1A/C 和 PHP1B 之间存在明显的临床重叠，但观察到疾病进展的差异。
