A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and skeletal abnormalities is caused by a novel activating parathyroid hormone (PTH)/PTH-related peptide receptor mutation

The Journal of Clinical Endocrinology and Metabolism
Murat BastepeDavid Gillis

Abstract

A novel heterozygous PTH/PTHrP receptor missense mutation (T410R) was identified in a male and his two sons who are all affected by a less severe form of Jansen's metaphyseal chondrodysplasia (JMC). JMC is a rare disorder that is typically characterized by severe growth plate abnormalities that lead to short-limbed dwarfism. Furthermore, affected individuals usually show significant hypercalcemia, despite normal or undetectable levels of PTH and PTHrP. In contrast, the three affected members of this new family showed only mild skeletal dysplasia, comparatively normal stature, and blood calcium concentrations either within or at the upper end of the normal range. However, PTH levels were suppressed, and urinary calcium excretion was elevated, which led to nephrolithiasis in both children. When expressed in COS-7 cells, the PTH/PTHrP receptor with the T410R mutation led to agonist-independent cAMP formation, which was less pronounced than that observed with the previously identified T410P mutant. Our findings indicate that a mild form of JMC has been identified that is characterized by less pronounced skeletal and laboratory abnormalities.

Citations

Aug 13, 2010·Cellular and Molecular Life Sciences : CMLS·Jean-Pierre VilardagaThomas J Gardella
Apr 25, 2012·Journal of Applied Genetics·Ivo MarikKazimierz Kozlowski
Jul 9, 2013·European Journal of Pharmacology·Federico MonczorCarlos Davio
Aug 13, 2010·Nature Reviews. Rheumatology·Eileen M Shore, Frederick S Kaplan
Dec 5, 2015·Expert Opinion on Orphan Drugs·Michael D BriggsKatarzyna A Pirog
Feb 8, 2005·Biochemical and Biophysical Research Communications·Robert C GensureHarald Jüppner
Jun 20, 2012·Trends in Pharmacological Sciences·Jean-Pierre VilardagaTimothy N Feinstein
Dec 5, 2013·Journal of Dental Research·S A Frazier-BowersS Bencharit
May 23, 2018·The Journal of Clinical Endocrinology and Metabolism·Hiroshi SaitoHarald Jüppner
Apr 19, 2007·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Erik Kern HarringtonKathy K H Svoboda
Sep 19, 2009·American Journal of Medical Genetics. Part a·Malwina Czarny-RatajczakKazimierz Kozlowski
Dec 4, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Erik Kern HarringtonKathy K H Svoboda
Aug 21, 2013·American Journal of Medical Genetics. Part a·Gianfranco SavoldiAlba Pilotta
May 16, 2014·The Journal of Clinical Endocrinology and Metabolism·Dong LiMichael A Levine
Feb 5, 2021·Scientific Reports·Alejandro García-CastañoSonia Gaztambide
May 16, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Caroline M Gorvin
Feb 8, 2005·Biochemical and Biophysical Research Communications·Sylvain Provot, Ernestina Schipani

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.