CYSTIC FIBROSIS BY CAROLINE KARUNYA PONNARASI KANGARAJ GROUP-IV 30-11-2010
INTRODUCTIONCystic fibrosis (also known as CF or mucoviscidosis) is acommon disease which affects the entire body, causingprogressive disability and often early death.The name cystic fibrosis refers to the characteristic scarring(fibrosis) and cyst formation within the pancreas, firstrecognized in the 1930s. Difficulty breathing is the mostserious symptom and results from frequent lung infectionsthat is treated with, though not cured by, antibiotics andother 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 GENELocus: 7q31.2 - The CFTR gene is foundin region q31.2 on the long (q) arm ofhuman chromosome 7.Gene Structure: The normal allelic variantfor this gene is about 250,000 bp long andcontains 27 exons.Gene Function: It is predicted that it codesa Integral membrane protein of about170kb know as CF TRANSMEMBRANECONDUCTANCE REGULATOR(CFTR)
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 • 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 GENEClass 1 mutations : Defective protein production withpremature termination of CFTR protein production.Class 1 mutations produce few or no functioningCFTR chloride channelsClass 2 mutations : Defective trafficking of CFTR sothat it does not reach the apical surface membranewhere it is intended to function Class 3 mutations : Defective regulation (openingand closing) of the CFTR chloride channel whichallows movement of chloride in and out of the celleven though the CFTR protein is able to reach theapical cell surface
Class 4 mutations: CFTR reaches theapical surface but conduction (passage ofchloride ions through the channel) isdefectiveClass 5 mutations : Associated withreduced synthesis of functional CFTRClass 6 mutations :proteins aresynthesized normally but are unstable atthe 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.
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 thinkings 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.