Posters S11trans with a 5 thymidines (5T) sequence within the intron 8 Splice Variant (IVS8) region.5T is responsible of an exacerbated skipping of exon 9, decreasing the functional product levels.It has been demonstrated that 5T phenotypic expression is influenced by another adjacent polymorphic region, constituted by 9 to 13 TG repeats.In particular, 5T/TG13 combination was found only in affected subjects.Case Report: We report a case regarding two sisters, aged 23 and 18 years, carriers of the F508del mutation associated with the 5T/TG13 combination.DHPLC investigation did not detect a second mutation.Both sisters present mild pulmonary symptoms started in puberty, bronchiectasis, pancreatic sufficiency and border-line chloride values at the sweat test.However, they differ because the elder patient has more evident bronchiectasis, and she also presents pansinusitis, a positive sputum culture and a slightly reduced FEV1.Conclusions: The natural history of non classic CF is poorly understood.It may be asymptomatic for years but a significant lung involvement may occur, as seen in the elder sister.This finding suggests that a prevention therapy could be necessary also in mild, non classic CF and an early diagnosis may prevent the organ deterioration, as in the younger sister.Early diagnosis may be supported by TG repeats testing in individuals carrying the 5T variant; in fact, our report confirms that the presence of 5T allele, in trans with a severe CFTR mutation, is associated with non classic CF and that TG13 variant acts as a real mild mutation, enhancing the 5T penetrance and determining the onset of a mild symptomatology in all patients.

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.

Background: Mutation spectra of the CFTR gene vary between populations.Knowledge of these mutation spectra is needed for diagnostic purposes, for counselling in CF families and for screening, either neonatal to improve prognosis, or preconceptional and prenatal to provide for reproductive options.There is only limited knowledge about the mutation spectra in migrant populations in Europe.Aims: To determine the identity and frequency of mutations found in Turkish and North-African CF patients and to determine the test-sensitivity of common CF-gene mutation panels when offering carrier screening to Mediterranean people.Methods: In a survey among 373 European CF-centres, we asked which mutations have been found among Turkish and North African CF patients.Results: Fifty mutations had been found on 75.2% (95% CI: 70.4 80.0%) of CFTR alleles of patients ( n 156) originating from Turkey or North Africa.The mean sensitivity of common CF-gene mutation panels to detect these mutations was 50.6% (95% CI: 45.0 56.2%), and differed significantly between Turkish and North-African people: 41.7% (95% CI: 34.7 48.6%) versus 66.4% (95% CI: 57.7 75.2%).A sensitivity of 63.6% (95%CI: 58.2 69.0) can be achieved by expanding the mutation panels with these Mediterranean mutations.Conclusion: A low test-sensitivity of common CF-gene mutation panels for carrier screening of Mediterranean people was observed.This raises questions on whether and how to implement CF-carrier screening in a multi-ethnic society.