CYSTIC FIBROSIS

BY CAROLINE KARUNYA PONNARASI KANGARAJ

GROUP-IV

30-11-2010

INTRODUCTION

Cystic 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 albeta

o 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 disease

Exocrine pancreatic insufficency

Obstructive azoospermia

Elevated sweat chloride concentration

Growth failure

Meconium 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