Lamellar ichthyosis (Lamellar ichthyosis) - Gen TGM1.
Lamellar ichthyosis is a disorder that primarily affects the skin. Typically, children with this disorder are born with collodion membrane. This membrane usually dried and off during the first weeks of life and is subsequently clear that newborns have scaly skin and eyelids and lips which are turned outwardly. A characteristic feature of lamellar ichthyosis is that those affected have large, dark, like flakes to plaques, the skin covering most of his body. Affected children may have infections, dehydration, respiratory problems, alopecia, nail dystrophy, hyperhidrosis, increased sensitivity to heat and keratoderma. Less frequently, affected individuals have erythema and joint deformities.
In approximately 90% of cases, this process is due to mutations in the gene TGM1. Mutations in other genes associated with lamellar ichthyosis are each responsible for only a small percentage of cases. In some people with lamellar ichthyosis, the cause of the disease is unknown. They have identified multiple chromosomal regions containing genes that may be associated with lamellar ichthyosis, although specific genes have not been identified.
The TGM1 gene, located on the long arm of chromosome 14 (14q11.2), encodes an enzyme called transglutaminase 1. This enzyme is found in the cells that form the epidermis and is involved in the formation of cornified envelope cell, which is structure it is covering skin cells and helps to form a protective barrier between the organism and its surroundings. Specifically, transglutaminase 1 forms strong bonds, called cross - links between structural proteins that make up the cell envelope cornea. This crosslinking provides strength and stability to the epidermis.
They have identified several mutations in the gene TGM1 result lamellar ichthyosis. Some mutations change in the enzyme transglutaminase nucleotide 1. The most frequent mutation (877-2A> G) affects encoding the enzyme leading to an abnormally short, nonfunctional enzyme. Other mutations result in a transglutaminase enzyme 1 can not operate normally, it is abnormally short, or no enzyme is encoded. Deficiency transglutaminase one functional inhibits the formation of the cell envelope cornea, causing anomalies in the lamellar ichthyosis skin.
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 lamellar ichthyosis, by complete PCR amplification of the exons of the gene TGM1 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).