Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study

Abstract

IntroductionCystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing.MethodsThis study reports the results of a molecular screening of cystic fibrosis using DNA samples of patients enrolled from January 2009 to December 2013. Patients were referred to our laboratory for cystic fibrosis screening for infertile couples. In addition, we identified the gene mutations present in 76 patients affected by cystic fibrosis in the pediatric population of Basilicata.ResultsIn the 964 infertile couples examined, 132 subjects (69 women and 63 men) resulted heterozygous for one of the CFTR mutations, with a recurrence of carriers of 6.85%. The recurrence of carriers in infertile couples is significantly higher from the hypothetical value of the general population (4%).ConclusionsThis study shows that in the Basilicata region of Italy the CFTR phenotype is caused by a small number of mutations.Our aim is to develop a kit able to detect not less than 96% of CTFR gene mutations so that the relative risk for screened couples is superimposable with respect to the general population.

Next-Generation Sequencing for Screening Analysis of Cystic Fibrosis: Spectrum and Novel Variants in a South–Central Italian Cohort

“…Differences among Italian regions are reported, with a frequency of 1:31 in northern Italy [8], 1:27 in the Lazio region (central Italy) [5], 1:16 in Sicily [34], and 1:14 in the Basilicata region [36] (southern Italy). In the present paper, we calculated a frequency of CF carriers of 1:12 (8%), which is higher than that expected for the Caucasian population and consistent with the studies of Chamayou et al (6%), analyzing CF carriers in Sicily using an NGS approach [33], and Dell'Edera et al, analyzing Basilicata CF carriers using whole-gene analysis (7%) [36]. We identified the typical CFTR p.(Phe508del) mutation in 37% of pathogenic variant carriers.…”

“…Similarly, the frequency of healthy CF carriers of a single mutation is estimated to be 1:25 in the Caucasian general population and is concordant with Italian carrier screening data. Differences among Italian regions are reported, with a frequency of 1:31 in northern Italy [ 8 ], 1:27 in the Lazio region (central Italy) [ 5 ], 1:16 in Sicily [ 34 ], and 1:14 in the Basilicata region [ 36 ] (southern Italy). In the present paper, we calculated a frequency of CF carriers of 1:12 (8%), which is higher than that expected for the Caucasian population and consistent with the studies of Chamayou et al (6%), analyzing CF carriers in Sicily using an NGS approach [ 33 ], and Dell’Edera et al, analyzing Basilicata CF carriers using whole-gene analysis (7%) [ 36 ].…”

Reports of Three Cases of Atypical Cystic Fibrosis with Azoospermia

“…Mutations in these genes may result in a defective activation of CFTR [10]. Not all patients with cystic fibrosis have abnormal sweat chloride levels, severe lung disease, or failure to thrive.…”

A Clinical and Molecular Survey of 62 Cystic Fibrosis Patients from Umbria (Central Italy) Disclosing a High Frequency (2.4%) of the 2184insA Allele: Implications for Screening

“…In fact, the incidence of the most frequent CFTR mutations differs between Italian regions. An analysis of the frequency and distribution of CF alleles in Italy has been carried out for several regions, but knowledge on mutation distribution is lacking for Umbria, a small and quite geographically isolated region with approximately 900,000 inhabitants situated in central Italy, which was not included in any of the previous surveys because the number of chromosomes tested was <50 [3,4,5,6,7,8,9]. In this study, we performed a comprehensive retrospective clinical and molecular survey of 62 CF patients (124 chromosomes) coming from this region.…”