Premium
Clinical and genetic characteristics of Pseudohypoparathyroidism in the Chinese population
Author(s) -
Chu Xueying,
Zhu Yan,
Wang Ou,
Nie Min,
Quan Tingting,
Xue Yu,
Wang Wenbo,
Jiang Yan,
Li Mei,
Xia Weibo,
Xing Xiaoping
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13516
Subject(s) - gnas complex locus , pseudohypoparathyroidism , medicine , gastroenterology , epilepsy , endocrinology , multiplex ligation dependent probe amplification , population , macrocephaly , missense mutation , pediatrics , parathyroid hormone , genetics , biology , mutation , psychiatry , exon , environmental health , gene , calcium
Summary Background 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. Objectives To obtain an overall view of the clinical and genetic characteristics of the Chinese PHP patient population. Methods 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 PHP 1A/C and PHP 1B patients. Results Ten PHP 1A/C, 21 familial PHP 1B and 73 sporadic PHP 1B patients were identified. Four novel GNAS mutations were discovered in these patients, including c.1038+1G>T, c.530+2T>C, c.880_883del CAAG and c.311_312del AAG , 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 PHP 1B (10%‐35%) and PHP 1A/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 PHP 1B and PHP 1A/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. Conclusions 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 PHP 1A/C and PHP 1B, differences in disease progression were observed.