SEARCH FOR MUTATIONS IN PANCREATIC SUFFICIENT CYSTIC-FIBROSIS ITALIANPATIENTS - DETECTION OF 90-PERCENT OF MOLECULAR DEFECTS AND IDENTIFICATION OF 3 NOVEL MUTATIONS

A cohort of 31 cystic fibrosis patients showing pancreatic sufficiency and bearing an unidentified mutation on at least one chromosome was a nalyzed through denaturing gradient gel electrophoresis of the whole c oding region of the cystic fibrosis transmembrane conductance regulato r gene, including intron-exon boundaries. Three new and 19 previously described mutations were detected. The combination of these with known mutations detected by other methods, allowed the characterization of mutations on 56/62 (90.3%) chromosomes. Among those identified, 17 can be considered responsible for pancreatic sufficiency, since they were found in patients carrying a severe mutation on the other chromosome. Among these presumed mild mutations, eight were detected more than on ce, R352Q being the most frequent in this sample (4.83%). Intragenic m icrosatellite analysis revealed that the six chromosomes still bearing unidentified mutations are associated with five different haplotypes. This may indicate that these chromosomes bear different mutations, ra refy occurring among cystic fibrosis patients, further underlying the molecular heterogeneity of the genetic defects present in patients hav ing pancreatic sufficiency.