Statistics from Altmetric.com
The common perception of cystic fibrosis (CF) is that of a recessive disorder presenting in infancy or early childhood with malabsorption and progressive lung disease. However, mild phenotypes have always been recognised. These individuals, who are pancreatic sufficient, present later, have less severe lung disease and significantly lower sweat Cl− concentrations. Following identification of the CF gene in 1989, it was realised that patients with a classic phenotype had severe mutations on both chromosomes, typically ΔF508 which is present in 70% of CF chromosomes, whereas mildly affected individuals had one or more mild alleles. To date, more than 700 mutations have been identified in the CF gene; most, with the exception of G551D, G542X and 621+1 (G-A) are rare, affecting <1% of CF chromosomes.
The CF gene codes for a cyclic adenosine monophosphate (cAMP) mediated Cl− channel which has been identified in several epithelia including lung, biliary tract, pancreas, and vas deferens.1 This wide distribution accounts for the multi-organ involvement seen in cystic fibrosis. Channel function is mutation specific with five basic classes of mutation recognised (fig1).2 Mutations that produce no CFTR protein (class I), where CFTR protein fails to reach the apical membrane because of defective processing (class II), or production of protein that fails to respond to cAMP (class III), have <1% channel function and display a severe phenotype with pancreatic insufficiency. Mutations that produce a cAMP responsive channel with reduced conductance (class IV) or mutations that cause reduced synthesis or partially defective processing of normal CFTR (class V) …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.