Molecular and clinical features associated with CFTR gene rearrangements in Italian population: identification of a new duplication and recurrent deletions

Abstract

Cystic fibrosis (CF) is mainly caused by small deletions or missense mutations in the CFTR gene. The CF mutation database lists more than 35 large rearrangements that may escape detection using polymerase chain reaction-base techniques. The Innogenetics assay, the denaturing high-performance liquid chromatography and sequencing screening showed a mutation detection rate of 92.6% in our population. We report here the results of multiplex ligation-dependent probe amplification (MLPA) screening for CFTR gene rearrangements, performed on the unidentified alleles of our CF patients. Our sample population consists of 692 non-related Italian CF patients (for a total of 1384 alleles), followed at CF Centres in the Lombardia Region. MLPA analysis was performed in 49 patients who still had one or two unidentified alleles (for a total of 52 unidentified alleles) after extensive analysis of CFTR gene. All patients who were studied had the classical form of CF. We characterized nine different deletions and a new duplication. The deletion of exons 22-23 (7/82) was the most frequent in our cohort. The search for deletion/duplications of the CFTR gene has made it possible to reach a 94.1% detection rate, with an improvement (1.6%) of the carrier detection rate in the Italian population.