Cystic fibrosis has an autosomal recessive pattern of inheritance CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, ΔF508, is a deletion (Δ signifying deletion) of three nucleotides that results in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%) of CF cases worldwide and 90% of cases in the United States; however, over 1500 other mutations can produce CF. Although most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an autosomal recessive disease. The CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long. More specifically, the location is between base pair 117,120,016 and 117,308,718 on the long arm of chromosome 7, region 3, band 1, subband 2, represented as 7q31.2. Structurally, the CFTR is a type of gene known as an ABC gene. The product of this gene (the CFTR protein) is a chloride ion channel important in creating sweat, digestive juices, and mucus. This protein possesses two ATP-hydrolyzing domains, which allows the protein to use energy in the form of ATP. It also contains two domains comprising six alpha helices apiece, which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase. The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction. The majority of CFTR in the lung's passages is produced by rare ion-transporting cells that regulate mucus properties. In addition, the evidence is increasing that genetic modifiers besides CFTR modulate the frequency and severity of the disease. One example is mannan-binding lectin, which is involved in innate immunity by facilitating phagocytosis of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections. Carriers Up to one in 25 individuals of Northern European ancestry is considered a genetic carrier. The disease appears only when two of these carriers have children, as each pregnancy between them has a 25% chance of producing a child with the disease. Although only about one of every 3,000 white newborns has CF, more than 900 mutations of the gene that causes CF are known. Current tests look for the most common mutations. The mutations screened by the test vary according to a person's ethnic group or by the occurrence of CF already in the family. More than 10 million Americans, including one in 25 white Americans, are carriers of one mutation of the CF gene. CF is present in other races, though not as frequently as in white individuals. About one in 46 Hispanic Americans, one in 65 African Americans, and one in 90 Asian Americans carry a mutation of the CF gene.
medical cause of Bronchiectasis
medical cause of Bronchiolitis
medical cause of Hemoptysis
medical cause of Acute bronchitis
symptom of Idiopathic pulmonary fibrosis
symptom of Bronchiectasis
complications of Bronchiolitis
medical cause of Bronchiolitis obliterans