Progression of Mineral Ion Abnormalities in Patients with Jansen's Metaphyseal Chondrodysplasia (original) (raw)
2018, The Journal of clinical endocrinology and metabolism
Five different activating PTH/PTHrP receptor (PTHR1) mutations have been reported as causes of Jansen metaphyseal chondrodysplasia (JMC), a rare disorder characterized by severe growth plate abnormalities and PTH-independent hypercalcemia. Assess the natural history of clinical and laboratory findings in twenty-four JMC patients and characterize the disease-causing mutant receptors in vitro. The H223R mutation occurred in 18 patients. T410P, I458R and I458K each occurred in single cases; T410R was present in a father and his two sons. Laboratory records were analyzed individually and in aggregate. Postnatal calcium levels were normal in most patients, but elevated between 0.15-10 years (11.8±1.37 mg/dL) and tended to normalize in adults (10.0±1.03 mg/dL). Mean phosphate levels were at the lower end of the age-specific normal ranges. Urinary calcium/creatinine (mg/mg) was consistently elevated (children: 0.80±0.40; adults: 0.28±0.19). Adult heights were well below the 3rd percentile ...
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Jansen's metaphyseal chondrodysplasia: a disorder due to a PTH/PTHrP receptor gene mutation
Trends in endocrinology and metabolism: TEM, 1996
Jansen's metaphyseal chondrodysplasia (JMC) is a rare genetic disorder that is characterized by short-limbed dwarfism and severe, agonist-independent hypercalcemia. An activating PTH/PTHrP receptor mutation that results in constitutive cAMP accumulation was recently identified in the genomic DNA of a patient with this disorder. These findings provide a plausible explanation for the abnormal regulation of growth-plate chondrocytes and mineral ion homeostasis in JMC, and may have significant implications for understanding the broader biological role of PTHrP and its receptor.
The Journal of clinical endocrinology and metabolism, 2016
Jansen's Metaphyseal Chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of parathyroid hormone (PTH). Five different heterozygous activating PTH/PTHrP receptor (PTH1R) mutations that change one of three different amino acid residues are known to cause JMC. Establishing the diagnosis of JMC during infancy or early childhood can be challenging, especially in the absence of family history and/or overt hypercalcemia. We therefore sought to provide radiographic findings supporting this diagnosis early in life. Three patients, a mother and her two sons, had radiographic evidence for JMC. However, obvious hypercalcemia and suppressed PTH levels were encountered only in both affected children. Sanger sequencing and endonuclease (SphI) digestion of PCR-amplified genomic DNA were performed to search for the H223R-PTH1R mutation. The heterozygous H223R mutation was identified...
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