Metaphyseal chondrodysplasia Jansen (Jansen metaphyseal chondrodysplasia JMC) - Gen PTH1R.
The metaphyseal chondrodysplasia Jansen (JMC) is a rare disorder characterized by a phenotype of low height and different bone abnormalities such as disruption of the metaphysis of long bones, metacarpal and metatarsal delayed chin, short fingers, spine, pelvis and distorted legs. In addition, affected individuals have hypercalcemia in the first years of life. At older ages, the bone development tends to normal, but with a marked deformation and dwarfism. In some individuals also often seen in the skull sclerosis can lead to hearing loss. This disease is also associated with normal or low serum parathyroid hormones two concentrations.
This process is due to mutations in the gene PTH1R, located on the short arm of chromosome 3 (3p22-p21.1). This gene encodes a protein that is a member of the family of G - protein coupled receptors 2. This protein is a receptor for parathyroid hormone (PTH) and the like parathyroid hormone (PTHLH) hormone. The activity of this receptor is mediated by G proteins that activate adenylate cyclase and phosphatidylinositol-calcium.
They have identified at least four different mutations in the gene in people with PTH1R metaphyseal chondrodysplasia Jansen (JMC). When expressed in vitro, mutations in the gene cause PTHR1 cAMP accumulation (cyclic AMP) independent of agonist. This gene is abundantly expressed in the kidney and bone, which serves as a mediator of the regulation of calcium levels and dependent phosphorus PTH and epiphyseal plate, which serves as a mediator of growth regulation and differentiation of chondrocytes dependent PTHrP. The presence of mutations in the PTHR1 gene cause constitutive activity, thus providing an explanation for the abnormal regulation of homeostasis of mineral ions and development of the epiphyseal plate in cases of JMC.
This disease is inherited as an autosomal dominant, which means that a copy of an altered gene in each cell is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with metaphyseal chondrodysplasia Jansen (JMC) using the complete PCR amplification of exons PTH1R gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).