[Cystic fibrosis: molecular update and clinical implications].
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic pneumopathy, pancreatic insufficiency, elevated sweat chloride levels and male infertility. It is caused by defects in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel. The identification of the CF-causing gene was a landmark in molecular medicine. Currently, over 1,300 disease-causing mutations have been reported to the Cystic fibrosis genetic analysis consortium. deltaF508 mutation is the most common CF allele, however a high heterogeneity of the CFTR mutations spectrum has been observed in populations, particularly in southern Europe and Latin America. Depending on the effect at the protein level, CFTR mutations can be divided in at least 5 classes. These mutations could cause totally (classes I-III) or partially (classes IV and V) loss of the protein function. The molecular defects resulting from different mutations in CFTR partially explain the clinical heterogeneity of the disease, suggesting the existence of modifier genes that are involved in modulating the phenotype and severity of the CF. In this review, we discuss the fundamental aspects and the recent progress that could give to the lector, the knowledge to understand the CFTR gene structure, the function of the CFTR protein, how CF mutations disrupt it, its phenotype consequences and finally, the strategies to design new therapies for the disease.
Orozco
Lorena
L
Laboratorio de Genómica de Enfermedades Multifactoriales, Instituto Nacional de Medicina Genómica, SS, México, DF. lorozco@inmegen.gob.mx
Chávez
Margarita
M
Saldaña
Yolanda
Y
Velázquez
Rafael
R
Carnevale
Alessandra
A
González-del Angel
Ariadna
A
Jiménez
Silvia
S
D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation; D010375:Pedigree
D019005:Cystic Fibrosis Transmembrane Conductance Regulator