Idiopathic pulmonary fibrosis (Idiopathic pulmonary fibrosis) - Genes TERC and TERT            

Idiopathic pulmonary fibrosis is a chronic progressive lung disease characterized by the formation of scar tissue (fibrosis), which prevents the diffusion of oxygen from the alveoli into the blood. Overall, the disease affects people between 50 and 70 years old.

Signs and symptoms of frequent idiopathic pulmonary fibrosis are shortness of breath, accompanied by persistent dry cough. Many affected individuals also show a loss of appetite and gradual weight loss. Some people with the disease develop the distal ends of the fingers and the flared and rounded feet (toes drumstick). Eventually, the scarring of the lungs increases until the lungs can no longer provide enough oxygen to organs and tissues. Some people develop other serious lung disorders, including lung cancer, pulmonary embolism, pneumonia or pulmonary hypertension. Most affected individuals survive between 3 to 5 years after diagnosis. However, the course of the disease is highly variable because some people affected seriously ill a few months, while others may live with the disease for a decade or more. In most cases, the disease occurs sporadically, affecting one person in a family. However, a small percentage of people with this disease have at least one other member of the affected family. When the disease occurs in several members of the same family, it is known as familial pulmonary fibrosis.

The cause of idiopathic pulmonary fibrosis is unknown, but the disease is likely due to a combination of genetic and environmental factors. It is likely that genetic changes increase the risk of developing idiopathic pulmonary fibrosis, with exposure to certain environmental factors. The environmental risk factors that could contribute to idiopathic pulmonary fibrosis include exposure to dust of wood or metal, viral infections, certain medications , and smoking.

Changes in several genes have been suggested as risk factors of idiopathic pulmonary fibrosis. Most of these genetic changes represent only a small proportion of cases. However, mutations in certain genes such as TERT TERC gene, located on the long arm of chromosome 3 (3q26), and located on the short arm of chromosome 5 (5p15.33) is found in approximately 15% of all cases of familial pulmonary fibrosis and a lower percentage of sporadic cases of idiopathic pulmonary fibrosis.

These genes encode the synthesis of a component of an enzyme called telomerase. Telomerase maintains structures called telomeres, which are composed of repeated DNA segments at the ends of chromosomes. Telomeres protect the chromosomes of the adhesion between them abnormally or they decompose. In most cells, the telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that causes cells to stop dividing and self - destruct. Telomerase counteracts the shortening of telomeres by adding small DNA repeated segments to the ends of chromosomes each time the cell divides.

Several mutations have been identified in the TERC gene and at least 23 mutations in the TERT gene in individuals with idiopathic pulmonary fibrosis. Mutations in TERC and TERT genes reduce or eliminate telomerase function, which causes the telomeres become too short as cells divide, so that the cells lining the inside of the lungs stop dividing or die prematurely. However, it is not known how shortened telomeres contribute to the formation of fibrosis and progressive lung damage characteristic of idiopathic pulmonary fibrosis.

Most cases of idiopathic pulmonary fibrosis are sporadic and occur in people with no history of disease in your family. In other cases, the disease appears to be an autosomal dominant inheritance, which means that a copy of an altered gene in each cell is sufficient to express the disease. However, some people who inherit the altered gene never develop the characteristics of familial pulmonary fibrosis, event called reduced penetrance. It is not clear why some people with a mutated gene develop the disease and others with the mutated gene no.

Tests in IVAMI: in IVAMI perform detection of mutations associated with idiopathic pulmonary fibrosis, by complete PCR amplification of the exons of TERC and TERT genes, respectively, 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).