Cystic fibrosis: Difference between revisions
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Class I: [[Premature Stop Codon|Premature Stop Codons]] (e.g. W1282X) | Class I: [[Premature Stop Codon|Premature Stop Codons]] (e.g. W1282X) | ||
Class II: [[Abnormal Processing|Abnormal Processing]] (e.g. ΔF508) <br>This involves the deletion of the [[Amino acid|amino acid]], [[Phenylalanine|Phenylalanine]] at NBD1 (Nucleotide Binding Domain 1) of the [[CFTR|CFTR]] (Cystic Fibrosis transmembrane conductance receptor). This mutation takes effect on the processing of the [[Protein|protein]] after leaving the Endoplasmic Reticulum. It adversely comprimises the trafficking/passage of the protein across the cytosol ultimately resulting in the the protein being degraded by the proteosome. This mutation is the most common mutation of the [[CFTR|CFTR]], causing >90% of [[Cystic_fibrosis|Cystic Fibrosis ]]cases <ref>J Biol Chem. 2010 Nov 12;285(46):35825-35. Epub 2010 Jul 28.</ref>. | Class II: [[Abnormal Processing|Abnormal Processing]] (e.g. ΔF508) <br>This involves the deletion of the [[Amino acid|amino acid]], [[Phenylalanine|Phenylalanine]] at NBD1 (Nucleotide Binding Domain 1) of the [[CFTR|CFTR]] (Cystic Fibrosis transmembrane conductance receptor). This mutation takes effect on the processing of the [[Protein|protein]] after leaving the [[Endoplasmic_Reticulum|Endoplasmic Reticulum]]. It adversely comprimises the trafficking/passage of the protein across the [[Cytosol|cytosol]] ultimately resulting in the the protein being degraded by the [[proteosome|proteosome]]. This mutation is the most common mutation of the [[CFTR|CFTR]], causing >90% of [[Cystic_fibrosis|Cystic Fibrosis ]]cases <ref>J Biol Chem. 2010 Nov 12;285(46):35825-35. Epub 2010 Jul 28.</ref>. | ||
Class III: [[Altered Regulation|Altered Regulation]] (e.g. G551D) | Class III: [[Altered Regulation|Altered Regulation]] (e.g. G551D) | ||
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Class IV: [[Conductance Defect|Conductance Defect]] (e.g. R117H) | Class IV: [[Conductance Defect|Conductance Defect]] (e.g. R117H) | ||
Class V: [[Reduced Protein Synthesis|Reduced Protein Synthesis]] (e.g. A455E)<ref>David L. Rimoin, J. Michael Connor, Reed E. Pyeritz, Bruce R. Korf (2007). Emery and Rimoin's Principles and Practice of Medical Genetics e-dition. 5th ed. Amsterdam: Elsevier. p1354-1394.</ref><br> | Class V: [[Reduced Protein Synthesis|Reduced Protein Synthesis]] (e.g. A455E)<ref>David L. Rimoin, J. Michael Connor, Reed E. Pyeritz, Bruce R. Korf (2007). Emery and Rimoin's Principles and Practice of Medical Genetics e-dition. 5th ed. Amsterdam: Elsevier. p1354-1394.</ref><br> | ||
== Approaches to Treatment == | == Approaches to Treatment == | ||
Revision as of 11:39, 1 November 2011
Cystic Fibrosis
Cystic Fibrosis is an autosomal recessive disease located on chromosome 7. Cystic Fibrosis is caused by a mutation to the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) channel. The most common mutation is ΔF508, accounting for 70% of mutations in the Caucasian UK population, in which the triplet code (codon) for the amino acid phenylalanine is deleted, disrupting Cl- transport. This mutation belongs to the Class II group of mutations causing Cystic Fibrosis.
CFTR is composed of 3 types of domains. There are 12 Transmembrane spanning domains, 2 Nucleotide Binding Domains (NBD’s) and an R domain (regulatory domain). The NBD’s are involved in the binding and hydrolysis of ATP.
CFTR is part of the ABC (ATP Binding Cassette) superfamily of transporters.
Cystic Fibrosis Classes
Class I: Premature Stop Codons (e.g. W1282X)
Class II: Abnormal Processing (e.g. ΔF508)
This involves the deletion of the amino acid, Phenylalanine at NBD1 (Nucleotide Binding Domain 1) of the CFTR (Cystic Fibrosis transmembrane conductance receptor). This mutation takes effect on the processing of the protein after leaving the Endoplasmic Reticulum. It adversely comprimises the trafficking/passage of the protein across the cytosol ultimately resulting in the the protein being degraded by the proteosome. This mutation is the most common mutation of the CFTR, causing >90% of Cystic Fibrosis cases [1].
Class III: Altered Regulation (e.g. G551D)
Class IV: Conductance Defect (e.g. R117H)
Class V: Reduced Protein Synthesis (e.g. A455E)[2]
Approaches to Treatment
Lung Function
Oral and Inhaled Antibotics
Pancreatic Function
Nutrional Regime