What happens to the protein in people with the F508 mutation?

The most common mutation in the gene associated with cystic fibrosis (CF) causes deletion of phenylalanine at residue 508 (delta F508) of the gene product called CFTR. This mutation results in the synthesis of a variant CFTR protein that is defective in its ability to traffic to the plasma membrane.

What is the R117H mutation?

R117H Mutation: The R117H mutation is generally considered to be a mild CF (class IV) mutation. When combined with another CF-causing variant it is associated with a broad phenotype, ranging from CF with suppurative lung disease, to no clinical disease.

What type of mutation is delta F508?

Cystic Fibrosis The most common mutation in the CFTR gene is ΔF508, a frameshift mutation caused by a three base-pair deletion at codon 508 in exon 10 of CFTR, resulting in the absence of a phenylalanine residue.

Is delta F508 a deletion?

The delta F508 is the most common defect in the cystic fibrosis (CF) gene; it involves in a 3-base deletion in codon 508 and results in the loss of a phenylalanine residue at amino acid position 508.

What does F508 deletion do?

The most common CF-causing mutation, the deletion of phenylalanine 508 (F508), is located in the N-terminal cytoplasmic NBD1 (5–9). This single amino acid deletion results in a dramatic reduction of mature, plasma membrane resident CFTR.

What is the most common CF mutation?

The most common CF mutation, F508del, is primarily considered to be a processing mutation. The F508del mutation removes a single amino acid from the CFTR protein.

What is the R334W mutation?

Abstract. Introdution: R334W is a poorly described mutation responsible for less severe forms of Cystic Fibrosis,compared to ΔF508. In small cohorts,R334W patients’ age at diagnosis was reported as higher and pancreatic insufficiency as less extent, but data on the impact of this mutation is lacking.

How common is the F508del mutation?

F508del is the most common of the more-than 1,400 CF mutations. Around 90% of the UK CF population carries at least one copy, and around 50% carries two.

Can cystic fibrosis shorten your life?

Outlook. Cystic fibrosis tends to get worse over time and can be fatal if it leads to a serious infection or the lungs stop working properly. But people with cystic fibrosis are now living for longer because of advancements in treatment. Currently, about half of people with cystic fibrosis will live past the age of 40.

What causes the F508del mutation?

The deletion of a phenylalanine at residue 508 (F508del) is the most common cause of CFTR misfolding leading to the disease. The F508del misfolding originates in the first nucleotide-binding domain (NBD1), which induces a global conformational change in CFTR through NBD1’s interactions with other domains.

What is the Delta F508 mutation and how does it cause CF?

If a person happens to have a two copies of this mutation then it causes cystic fibrosis (CF) which is responsible for approximately two third of the cases. The major signs and symptoms of the cystic fibrosis caused due to the delta f508 mutation are established and include the following;

How does the ΔF508-CFTR mutation affect channel opening rate?

Most, although not all, studies indicate that human ΔF508-CFTR manifests a gating defect mainly caused by a decreased opening rate. 356–362 Based on the gating mechanism of CFTR discussed previously, there are at least three possibilities that may explain how the ΔF508 mutation decreases the channel opening rate.

What is the relationship between ΔF508 and G551D mutations in NBD1?

Although ΔF508 appears to exert a negligible effect on the overall static structure of NBD1, 233,234 it may cause significant changes in the NBD1-ICL4 interaction dynamics. Another extensively studied mutation, G551D, is located at NBD1’s signature sequence.