MINI REVIEW article
Front. Endocrinol.
Sec. Cellular Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1641292
This article is part of the Research TopicGenetic and Molecular Determinants in Bone Health and Diseases - Volume IIView all 8 articles
Human diseases caused by homozygous PTH1R mutations
Provisionally accepted
- 1Washington University in St. Louis, St. Louis, United States
- 2Massachusetts General Hospital, Boston, United States
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The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled receptor that mediates the actions of parathyroid hormone in the regulation of blood calcium levels, as well as PTH-related protein (PTHrP) in the regulation of skeletal development. Severe loss-of-function homozygous mutations in PTH1R are incompatible with life as in Blomstrand's lethal chondrodysplasia, characterized by accelerated ossification. More recently, homozygous mutations located in the transmembrane, extracellular domains and C-tail of the PTH1R were identified in patients with milder conditions characterized by variable degrees of skeletal and mineral abnormalities. These include delayed ossification in Eiken syndrome, hypocalcemia in a pseudohypoparathyroidism-like disorder, and non-syndromic primary failure of tooth eruption; however, most PFTE cases are caused by heterozygous PTH1R mutations. Recent detailed pharmacologic characterization of these PTH1R mutants has revealed new insights into how even subtle perturbations in PTH1R function can result in disease.
Keywords: PTH1R, Blomstrand, Eiken, Tooth Eruption, Growth Plate, Delayed ossification, βArrestin, GPCR
Received: 04 Jun 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Portales-Castillo, Höppner, Jueppner and Gardella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ignacio Portales-Castillo, Washington University in St. Louis, St. Louis, United States
Thomas J Gardella, Massachusetts General Hospital, Boston, United States
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