Cystic fibrosis based on genetics

1. CYSTIC FIBROSIS
BY CAROLINE KARUNYA PONNARASI KANGARAJ
GROUP-IV
30-11-2010

2. 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.

3. 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

4. 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

6. 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

7. The cftr gene

8. THE CFTR GENE
Locus: 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)

9. THE CFTR PROTEIN

10. 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.

12. MUTATION IN THE CFTR POLYPEPTIDE

13. 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.

15. CLASSES OF CF GENE

16. 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

17. 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.

19. 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.

20. MAJOR PHENOTYPIC FEATURES
Progressive pulomonary disease
Exocrine pancreatic insufficency
Obstructive azoospermia
Elevated sweat chloride concentration
Growth failure
Meconium ileus.

21. 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

25. DIAGONOSIS
 Cystic fibrosis may be diagnosed by many
different categories of testing including :
• newborn screening,
• sweat testing, or genetic testing

26. 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.

27. 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.

28. THANK YOU