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

2015-01-13

azim58 - Notes on cystic fibrosis genetics and pathogenesis 2-3-13

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

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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.

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

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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.

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

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

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Class IV mutations: Defective conduction

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Class V mutations: Reduced number of active CFTR

gene modifiers
• TGF-beta 1
• MBL

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

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

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