[PDF] CFTR MUTATION CLASSES Normal Class I Class II Class III Class

CFTR MUTATION CLASSES Normal Class I Class II Class III Class

CFTR mutations are grouped into classes based on the way the mutations affect the CFTR protein The reverse side of this sheet shows the most common CFTR mutation classes In the future, mutations may also be classified by “theratype,” meaning which type of CFTR modulator therapy they respond to best

CFTR MUTATION CLASSES Normal Class I Class II Class III Class

CFTR mutations are grouped into classes based on the way the mutations affect the CFTR protein The reverse side of this sheet shows the most common CFTR mutation classes In the future, mutations may also be classified by “theratype,” meaning which type of CFTR modulator therapy they respond to best

THE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF)

•CF occurs when a child inherits two copies of a CFTRgene mutation resulting in a CF genotype1,2 •CFTR protein activity is determined by CFTR protein quantity and function1,3 •In CF, there is a reduction in total CFTR protein activity leading to an imbalance of fluid and ions in organs throughout the body1,3,4

Cystic Fibrosis Mutation Analysis - Oklahoma

However, over 1500 CFTR mutations have been documented worldwide This panel provides approximate CFTR mutation detection rates of 90 5 in North American Caucasians, 73 8 in Hispanic Americans, 67 5 in African Americans, 48 9 in Asian Americans, and 94 0 in Ashkenazi Jews based on reported mutation frequencies in ethnic groups

Therapeutic Class Overview Cystic fibrosis transmembrane

either reduce the amount of CFTR protein that reaches the cell membrane surface or reduce the function of CFTR as a chloride channel (Egan 2016) The most common CFTR mutation leading to CF is the F508del mutation; approximately 50 of patients with CF are homozygous for this mutation, and 90 carry at least 1 copy (Katkin 2019)

1 Introduction - WHO

CFTR gene mutations have been well characterized in most European populations In several Western-European countries, mutations are detected in more than 95 of the CFTR genes derived from CF patients The F508del CFTR mutation is the most common mutation causing CF F508del Frequencies vary from a

State of California—Health and Human Services Agency

CFTR modulators are new therapies that improve chloride transport across the cell membrane by modulating the structure and function of the defective CFTR There are over 1,700 known CFTR mutations Mutation classes amenable to current CFTR therapies include gating mutations, conduction mutations, splice mutations, protein-

[PDF] test mucoviscidose adulte

[PDF] mucoviscidose a 2 ans

[PDF] mucoviscidose symptômes

[PDF] test mucoviscidose naissance est il fiable

[PDF] mucoviscidose nourrisson début encombrement

[PDF] espérance de vie mucoviscidose 2016

[PDF] comment meurt-on de la mucoviscidose

[PDF] mucoviscidose age moyen décès

[PDF] gregory lemarchal

[PDF] fonction technique d'un vélo

[PDF] fonction d'usage d'un tramway

[PDF] symptome mucoviscidose tardive

[PDF] fonction technique d'un bateau

[PDF] fonction d'usage d'un bateau a moteur

[PDF] fonction d'usage d'une voiture wikipedia

CFTR MUTATION CLASSES

Class II Class III Class IV Class VClass INormal

DESCRIPTION

No functional

CFTR is created.CFTR protein

is created, but misfolds, keeping it from moving to the cell surface.CFTR protein is created and moves to the cell surface, but the channel gate does not open properly.CFTR protein is created and moves to the cell surface, but the function of the channel is faulty.Normal CFTR protein is created and moves to the cell surface, but in insufficient quantities.CFTR protein is created, moves to the cell surface and allows transfer of chloride and water.

Misfolded

proteinChannel gate does not openFaulty channelNot enough

CFTRWHAT'S HAPPENING IN THE CELLRNARibosomeNewly

folded

CFTRMature

CFTR channel

Airway

surface

MUTATION

EXAMPLES

G542X

W1282X

R553X aka “production mutations," which include nonsense mutations, some splice mutations and deletions G551D S549N aka “gating mutations"

Correctors such

as lumacaftor or tezacaftor help defective CFTR fold correctlyPotentiators such as ivacaftor help open the CFTR channel, and also help increase the function of normal CFTRRead-through compounds may allow production of full-length CFTR for nonsense mutations

POTENTIAL

THERAPIESCell

nucleus DNA

Cl-Cl-Cl-

22%88%6%6%5%

% of people with CF who have at least one mutation in that class No mutationF508del

N1303K

I507del

aka “processing mutations"

D1152H

R347P R117H aka “conduction mutations"

9/7/2017

3849+10kbCT

2789+5G

A A455E includes some splice mutations

Shortened

protein

Potential therapies

for CFTR mutations

Potentiators are drugs that

help open the CFTR channel at the cell surface and increase chloride transport.

Correctors are drugs that help the

defective CFTR protein fold properly so that it can move to the cell surface.

RNA therapies aim to either fix the

incorrect instructions in defective RNA, or provide normal RNA directly to the cell.

Gene-editing techniques aim to

repair the underlying genetic defect in the CF gene DNA. Gene replacement techniques aim to provide a correct copy of the CFTR gene.Read-through compounds aim to allow full-length CFTR protein to be made, even when the RNA contains a mutation telling the ribosome to stop.quotesdbs_dbs2.pdfusesText_2