What does Delta F508 mean?

Background and aims: Deletion of the codon for phenylalanine at position 508 (DeltaF508) is the most frequent disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

What causes delta 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.

Where is Delta F508 located?

In a modeled structure of CFTR, the residue F508 is found to be located in the NBD1-ICL4 interface where a cluster of aromatic residues is formed by amino acids from both NBD1 and ICL4.

What happens in Delta F508 mutation?

The most common (>90%) mutation in CF, a deletion of phenylalanine 508 (ΔF508), causes improper folding of the CFTR protein, resulting in its retention in the endoplasmic reticulum and proteosomal degradation.

What is F508del 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. Without this building block, the CFTR protein cannot stay in the correct 3-D shape.

What is Fibrosi?

In technical terms, fibrosis means thickening or scarring of the tissue. In this case, the normally thin, lacy walls of the air sacs in the lungs are no longer thin and lacy, but get thick, stiff and scarred, which is also known as fibrotic.

How does the Delta F508 mutation affect the body?

Delta f508 mutation is an inherited disease followed by the autosomal recessive pattern of mutations. This mutation is the deletion of three nucleotides which results in the defected manufacturing of the protein by the loss of amino acid phenylalanine at the 508 th position in this specified protein.

How many cases of CF are caused by mutations in F508?

Although deletion of F508 (ΔF508) in NBD1 constitutes ∼90% of all CF cases, more than 1500 disease-associated mutations of this 1480-amino acid protein have been described ( http://www.genet.sickkids.on.ca/cftr ).

Where did the cystic fibrosis deletion ΔF508 originate?

The other cystic fibrosis cases are the result of more than 500 different mutations, which makes genetic screening difficult. The distribution and relatively high frequency of the ΔF508 deletion suggest that it originated in Western Europe, perhaps around 2000 years ago, and has been positively selected.

Why is ivacaftor not effective for patients with ΔF508?

It was hypothesized that ivacaftor’s limited effects in patients homozygous for ΔF508 was related to the processing defect of CFTR. That is, the ΔF508 mutation causes a trafficking defect whereby the CFTR protein never reaches the cell surface where it can be effectively acted on by ivacaftor.