Donohue syndrome ... (Donohue syndrome) - Gen INSR.
Donohue syndrome is a rare disorder characterized by severe insulin resistance, an alteration in the tissues and organs of the organism do not respond properly to the hormone insulin. Insulin helps regulate blood sugar levels in the blood by controlling glucose levels passing blood cells to be used as energy. Severe insulin resistance causes problems with the regulation of glucose concentrations in the blood and affects the development and function of organs and tissues throughout the body.
Some of the signs and symptoms of the disease include short stature before birth, lack of growth and weight gain at the expected rate, lack of subcutaneous fat, muscle atrophy, hirsutism, multiple cysts in the ovaries in women and increased the size of the nipples, genitals, kidneys, heart and other organs. In addition, most affected individuals also have a skin disorder called acanthosis nigricans, where the skin folds of the body becomes thick, dark and velvety. Other signs include facial distinctive bulging eyes, thick lips, nose up and low - set ears. Affected individuals develop from childhood recurrent life - threatening infections.
Donohue syndrome is one of a group of related disorders known as severe hereditary syndromes insulin resistance. These changes, which also include Rabson-Mendenhall syndrome, among others, are considered part of a syndromic spectrum. Donohue syndrome represents the most severe end of the spectrum. Children with this condition do not survive beyond 2 years of age.
This alteration is due to mutations in the gene INSR, located on the short arm of chromosome 19 (19p13.3-p13.2). This gene encodes a protein called insulin receptor, which is found in many cell types. Insulin receptors are located in the outer membrane surrounding the cell, where they bind to circulating insulin in the bloodstream. This triggers signaling pathways that influence many cellular functions.
Mutations in the gene INSR, reduce the number of insulin receptors reaching the cell membrane or alter the function of these receptors greatly. Although insulin is present in the bloodstream without functional receptors can not carry out their effects on cells and tissues. This resistance to the effects of insulin affects the regulation of blood glucose and affects many aspects of development in people with the disease.
This disease is inherited in an autosomal recessive pattern, which means that 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 Donohue syndrome, by complete PCR amplification of the exons of the gene INSR, 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).