TY - JOUR T1 - Genotype-phenotype correlation in cystic fibrosis patients bearing a novel complex allele JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4297 AU - Riccardina Tesse AU - Angela Polizzi AU - Teresa Santostasi AU - Anna Diana AU - Antonio Manca AU - Vito Paolo Logrillo AU - Luciano Cavallo Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4297.abstract N2 - Objective: The genotype-phenotype relationship in cystic fibrosis (CF) patients bearing a novel transmembrane conductance regulator (CFTR) complex allele was investigated.Cases report: During the genetic characterization of 289 CF Caucasian patients [M/F ratio 0.9:1, median age 16 years (range 1-46)] we found a new complex allele [H939R;H949L] in five unrelated male patients (age range 15-25 years). They all carried two CF-associated mutations, H939R and H949L, on the same exon 15 of CFTR gene in one allele, and had R248T, G542X, 1259insA, G1349D and F508del, respectively, in the other allele. All subjects had abnormal sweat chloride test values. The patient with R248T/[H939R;H949L] genotype showed CF-related symptoms restricted exclusively to hepatopathy with high levels of transaminases, but a good nutritional status and pancreatic sufficiency. The other four patients had signs of classic CF, including chronic lung and sinus disease, recurrent respiratory infections, failure to thrive and pancreatic insufficiency. Particularly, patient with 1259insA/[H939R;H949L] genotype presented with meconium ileus, and the subject bearing F508del/[H939R;H949L] showed the most severe pulmonary manifestation of CF with abnormal values on tests of lung function.Conclusion: Our findings suggest that the allele [H939R;H949L] greatly reduces the residual function of CFTR if on the other allele is present a severe mutation (i.e., G542X, 1259insA, G1349D and F508del), determining a very low residual function, the combined effect being an overall reduction of CFTR function; on the contrary, when the other allele carries a mild mutation, such as R248T, the overall effect is a cumulative better CFTR functioning. ER -