Notes+on+cystic+fibrosis+genetics+and+pathogenesis+2-3-13

there's a specific database q The Cystic Fibrosis Mutation Database lists more than 1300 different mutations in the CFTR gene with potential to cause disease.

q The most common mutation is delta F508 (deletion of three DNA bases coding for the 508th amino acid residue phenylalanine), which is found in approximately 70 percent of Caucasian patients with CF in the United States.

q Mutations of the CFTR gene have been divided into five different classes

q Class I mutations: Defective protein production — This defect is usually caused by nonsense, frameshift, or splice-site mutations, leading to premature termination of the mRNA and complete absence of CFTR protein.

q Class II mutations: Defective protein. . . which prevents the protein from trafficking to the correct cellular location

q Class III mutations: Defective regulation ^doesn't respond to ATP as well

q Class IV mutations: Defective conduction

q Class V mutations: Reduced number of active CFTR

gene modifiers • TGF-beta 1 • MBL

q In approximately 10 percent of patients with suspected CF, the disease manifestations appear to be unusually mild or limited to one organ system

q tissue destruction in a process known as "prolonged endobronchial protease activity"