Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


CF (Cystic fibrosis) - CFTR Gene

Cystic fibrosis (CF) is a genetic disorder that primarily affects the lungs, and to a lesser extent the pancreas, liver and intestine, causing the accumulation of thick mucus adherent in these areas. Conditions associated with cystic fibrosis often are pancreatic insufficiency, obstructive respiratory disease, nutritional problems , and reproductive problems.

Cystic fibrosis often manifest in childhood, although in some cases (4%) are diagnosed in adulthood. About 20% has meconium ileus at birth, and other chronic respiratory disorders present, stunting or both. Between 5 and 15% of patients do not develop pancreatic insufficiency. Over 95% of men have azoospermia due to congenital absence of the vas deferens. In addition, women with cystic fibrosis may have complications in pregnancy. The major determinant of morbidity and mortality of this disease is respiratory failure and right ventricular failure secondary to the destruction of the lung parenchyma and elevated pulmonary vascular resistance. Median survival is 33 years, although symptomatic treatment advances are increasing the longevity and currently have a next life expectancy at 40 years.

The cause of cystic fibrosis, CFTR gene, is located on the long arm of chromosome 7 (7q31.2) and includes 27 exons with a size of 250 kb mRNA result in a 6500 bp of. This gene encodes the CFTR protein, amino acids 1480 and 168-kDa molecular weight. CFTR is a chloride channel regulated by cAMP, which regulates other ion channels. CFTR maintains hydration of secretions in the airway passages and through the transportation of chlorine and the inhibition of the uptake of sodium. Therefore, as we have described, CFTR dysfunction affects many organs and especially the upper and lower respiratory tract, the pancreas, the biliary system, the intestine, male genitalia and the sweat glands.

So far we have identified more than 1,400 CFTR mutations in the gene that cause cystic fibrosis. Most CFTR gene mutations responsible for cystic fibrosis change individual amino acids in the CFTR protein or eliminate a small amount of DNA of the CFTR gene. The most frequent mutation is a deletion of three base pairs causes loss of the phenylalanine at position 508 of the gene, exon 10. These genetic changes alter the coding, structure, or stability of the chloride channel. The resulting abnormal channel breaks shortly after generated, so never reaches the cell membrane for the transport of chloride ions. As a result, cells lining the ducts of the lungs, pancreas and other organs produce abnormally thick, tenacious mucus. Abnormal mucus clogs the airways and glands, causing the characteristic signs and symptoms of cystic fibrosis.

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 cystic fibrosis, by complete PCR amplification of the exons of the CFTR gene, and subsequent sequencing. We recommend starting the study by exon 10, where most of the mutations responsible for cystic fibrosis are located.

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) if postnatal diagnosis. For prenatal diagnosis, amniocentesis or chorionic villi.