Insensitivity to growth hormone (Growth Hormone Insensitivity) - Gen GHR.
Insensitivity to growth hormone, also known as insensitivity to growth hormone (GHIS) syndrome, is a severe form of non-response to growth hormone characterized by impaired growth, short stature, hormone receptor dysfunctional growth and failure to generate factor I insulin - like in response to growth hormone growth.
This process is due to changes in the GHR gene, located on the short arm of chromosome 5 (5p13-p12). This gene encodes a transmembrane receptor of growth hormone from the pituitary gland involved in regulating postnatal body growth. The binding of growth hormone to the receptor leads to receptor dimerization and activation of a transduction pathway intra and intercellular signal leading to growth.
Heterozygous mutations have been identified and compound heterozygous people with insensitivity to growth hormone. Mutations in this gene have been associated with Laron syndrome, idiopathic short stature (ISS) and insensitivity to growth hormone (GHIS) syndrome. In humans the binding protein growth hormone (GHBP) is generated by proteolytic cleavage of the binding domain extracellular ligand receptor protein hormone mature growth. Certain alterations in the GHR gene, create resistance or complete insensitivity to GH action (IGH), which is defined and characterized at the molecular level as Laron syndrome. These patients have reduced or absent expression of GHR gene in the liver, serum GH high, IGF-I greatly diminished and the serum concentration of GHBP is low indicating peripheral insensitivity to GH.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with insensitivity to growth hormone by the complete PCR amplification of the GHR gene exons 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).