期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 33, 期 8, 页码 1480-1488出版社
WILEY
DOI: 10.1002/jbmr.3450
关键词
PSEUDOHYPOPARATHYROIDISM; PSEUDOPSEUDOHYPOPARATHYROIDISM; GNAS; EARLY-ONSET OBESITY; GROWTH
资金
- recurrent INSERM funding
- Ipsen [8NL7]
- FECYT, MINECO
- National Institutes of Health [RO1 DK46718, PO1 DK11794, K23 DK101689]
- Instituto de Salud Carlos III (Institute of Health Carlos III) of the Ministry of Economy and Competitiveness (Spain)
- European Regional Development Fund [PI16-00073]
- Department of Health of the Basque Government [GV2016/111105]
- French Society of Pediatric Endocrinology and Diabetology (SFEDP)
- Sandoz
- SFEDP
- Pfizer
- Lilly
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000445, UL1TR002243] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK046718, P01DK011794, K23DK101689] Funding Source: NIH RePORTER
Pseudohypoparathyroidism type 1A (PHP1A), pseudoPHP (PPHP), and PHP type 1B (PHP1B) are caused by maternal and paternal GNAS mutations and abnormal methylation at maternal GNAS promoter(s), respectively. Adult PHP1A patients are reportedly obese and short, whereas most PPHP patients are born small. In addition to parathyroid hormone (PTH) resistance, PHP1A and PHP1B patients may display early-onset obesity. Because early-onset and severe obesity and short stature are daily burdens for PHP1A patients, we aimed at improving knowledge on the contribution of the GNAS transcripts to fetal and postnatal growth and fat storage. Through an international collaboration, we collected growth and weight data from birth until adulthood for 306 PHP1A/PPHP and 220 PHP1B patients. PHP1A/PPHP patients were smaller at birth than healthy controls, especially PPHP (length Z-score: PHP1A -1.1 +/- 1.8; PPHP -3.0 +/- 1.5). Short stature is observed in 64% and 59% of adult PHP1A and PPHP patients. PHP1B patients displayed early postnatal overgrowth (height Z-score at 1 year: 2.2 +/- 1.3 and 1.3 +/- 1.5 in autosomal dominant and sporadic PHP1B) followed by a gradual decrease in growth velocity resulting in normal adult height (Z-score for both: -0.4 +/- 1.1). Early-onset obesity characterizes GNAS alterations and is associated with significant overweight and obesity in adults (bodey mass index [BMI] Z-score: 1.4 +/- 2.6, 2.1 +/- 2.0, and 1.4 +/- 1.9 in PPHP, PHP1A, and PHP1B, respectively), indicating that reduced Gs alpha expression is a contributing factor. The growth impairment in PHP1A/PPHP may be due to Gs alpha haploinsufficiency in the growth plates; the paternal XL alpha s transcript likely contributes to prenatal growth; for all disease variants, a reduced pubertal growth spurt may be due to accelerated growth plate closure. Consequently, early diagnosis and close followup is needed in patients with GNAS defects to screen and intervene in case of early-onset obesity and decreased growth velocity. (c) 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据