CYSTIC FIBROSIS

BY CAROLINE KARUNYA PONNARASI KANGARAJGROUP-IV

30-11-2010

INTRODUCTIONCystic fibrosis (also known as CF or mucoviscidosis) is a common disease which affects the entire body, causing progressive disability and often early death.

The name cystic fibrosis refers to the characteristic scarring (fibrosis) and cyst formation within the pancreas, first recognized in the 1930s. Difficulty breathing is the most serious symptom and results from frequent lung infections that is treated with, though not cured by, antibiotics and other medications.

WHAT IS CYSTIC FIBROSIS ?

Chronic progressive life limiting Autosomal recessive genetic disease characterized

by : chronic respiratory disease pancreatic insufficiency elevation of sweat electrolytes and male infertility

GENETICS IN CYSTIC FIBROSIS

Cystic fibrosis is a heterogeneous recessive genetic disorder with features that reflect mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene .

CYSTIC FIBROSIS

CLASSIC NON-CLASSIC

DISEASE ETIOLOGY AND INCIDENCE

• CF has been in all races ,it is predominately o diseases of northern europeans.

• The live birth incidence of CF ranges from :o 1in 313 among the Hutterites of southern albetao Canada,to 1 in 90,000 among the asian

population of hawaii.o Among all U.S whites,the diseases is 1 in 3200

The cftr gene

THE CFTR GENELocus: 7q31.2 - The CFTR gene is found in region q31.2 on the long (q) arm of human chromosome 7. Gene Structure: The normal allelic variant for this gene is about 250,000 bp long and contains 27 exons.Gene Function: It is predicted that it codes a Integral membrane protein of about 170kb know as CF TRANSMEMBRANE CONDUCTANCE REGULATOR(CFTR)

THE CFTR PROTEIN

THE CFTR PROTEIN

CFTR transports chloride ions (Cl-) ions across the membranes of cells in the lungs, liver, pancreas, digestive tract, reproductive tract, and skin.

The CFTR chloride channels has FIVE DOMAINS:

1. Two membrane –spanning domains : Each with six transmembrane sequences;

2. Two nucleotide(ATP)-binding domains;

3. Regulatory domain with multiple phosphorylation site.

MUTATION IN THE CFTR POLYPEPTIDE

MUTATION IN THE CFTR POLYPEPTIDE

• The first mutation identified ,a deletion of a phenylalanine residue at position 508 in the first ATP- binding fold,is the most common defect, accounting for about 70% of all CF alleles in white populations.

• In these population ,only seven other mutation are more frequent than 0.5%,and the remainder are therfore are rare.

CLASSES OF CF GENE

CLASSES OF CF GENE

Class 1 mutations : Defective protein production with premature termination of CFTR protein production. Class 1 mutations produce few or no functioning CFTR chloride channels

Class 2 mutations : Defective trafficking of CFTR so that it does not reach the apical surface membrane where it is intended to function

Class 3 mutations : Defective regulation (opening and closing) of the CFTR chloride channel which allows movement of chloride in and out of the cell even though the CFTR protein is able to reach the apical cell surface

Class 4 mutations: CFTR reaches the apical surface but conduction (passage of chloride ions through the channel) is defective

Class 5 mutations : Associated with reduced synthesis of functional CFTR

Class 6 mutations :proteins are synthesized normally but are unstable at the cell surface.

PATHOPHYSIOLOGY OF CYSTIC FIBROSIS

• CF is due to abnormal fluid and electrolyte transport across epithelial apical membranes.

• This abnormality leads to disease in the Lung , Pancreas, Intestine, Hepatobiliary tree and male genital tract.

MAJOR PHENOTYPIC FEATURES

Progressive pulomonary diseaseExocrine pancreatic insufficencyObstructive azoospermiaElevated sweat chloride concentrationGrowth failureMeconium ileus.

SYMPTOMS

Thick mucus in secretion in the lungs Repeated Infection ( the accumulation of sticky , thick

mucus in the lungs creates a favorable environment for infectious microorganism to inhabit and flourish)

Stools , pale or clay coloured , foul smelling or stools that float

Bronchitis , Pneumonia ,nasal polyps Excessive salt in sweat Enlarged finger tips-clubbing

DIAGONOSIS Cystic fibrosis may be diagnosed by many

different categories of testing including :• newborn screening, • sweat testing, or genetic testing

TREATMENT• The only way to cure CF would be to use gene therapy to

replace the defective gene or to give the patient the normal form of the protein before symptoms cause permanent damage.

• The major goal in treating CF is to clear the abnormal and excess secretions and control infections in the lungs, and to prevent obstruction in the intestines.

• For patients with advanced stages of the disease, a lung transplant operation may be necessary.

• Although treating the symptoms does not cure the disease, it can greatly improve the quality of life for most patients and has, over the years, increased the average life span of CF patients to 30 years.

CONCLUSION“Woe is the child who tastes salty from a kiss on the

brow, for he is cursed , and soon must die” After coming to know about these diseases

and the worst thinking's of the mankind about a child ,I think you would have got the motivation to live long and stay strong for anything and you will realize that your life is not that tough compare to those who are suffering from an incurable diseases.Till now doctors all around through world are still finding medicine and ways to cure this diseases .I wish that someone here in the classroom will be the first one who finds the cure for Cystic fibrosis in the future and help kids like who are undergoing these unwanted sayings.

THANK YOU