Background Cystic fibrosis (CF) has a vast and heterogeneous mutational spectrum in Europe. This variability has also been described in Spain, and there are numerous studies linking CFTR variants with the symptoms of the disease. Most of the studies analysed determinate clinical manifestations or specific sequence variants in patients from clinical units. Others used registry data without addressing the genotype–phenotype relationship. Therefore, the objective of this study is to describe the genetic and clinical characteristics of people with CF and to analyse the relationship between both using data from the rare disease registry of a region in southeastern Spain. Methods A cross-sectional study was carried out in people with a confirmed diagnosis of CF registered in the Rare Diseases Information System (SIER) of the Region of Murcia (Spain). The patients were classified into two genotypes according to the functional consequence that the genetic variants had on the CFTR protein. Results There were 192 people diagnosed with CF reported in the Region of Murcia as of 31 December 2018. Seventy-six genotypes and 49 different variants were described, with c.1521_1523delCTT (p. Phe508del) being the most common in 58.3% of the CF patients and 37.0% of the alleles. In addition, 67% of the patients were classified as a high-risk genotype, which was associated with a lower percentage of FEV1 (OR: 5.3; 95% CI: 1.2, 24.4), an increased risk of colonization by Pseudomonas aeruginosa (OR: 7.5; 95% CI: 1.7, 33.0) and the presence of pancreatic insufficiency (OR: 28.1; 95% CI: 9.3, 84.4) compared to those with a low-risk genotype. Conclusions This is the first study in Spain that describes the mutational spectrum and its association with clinical manifestations in patients with CF using data from a rare disease registry. The results obtained allow planning for the health resources needed by people with this disease, thus contributing to the development of personalized medicine that helps to optimize health care in CF patients.

Background: Cystic fibrosis (CF) has a very heterogeneous mutational spectrum in Europe. This variability has also been described in Spain, and there are numerous studies that relate CFTR variants with the symptoms of the disease. Most of them analyze determinate clinical manifestations or specific sequence variants in patients from clinical units. Others use registry data without addressing the genotype-phenotype relationship. Therefore, the objective of this study is to describe the genetic and clinical characteristics of people with CF, and to analyze the relationship between both, using data from the rare diseases registry of a region in southeastern Spain.Methods: A cross-sectional study was carried out in people with a confirmed diagnosis of CF registered in the Rare Diseases Information System (SIER) of the Region of Murcia (Spain). The patients were classified into two genotypes according to the functional consequence that the genetic variants had on the CFTR protein.Results: There were 192 people diagnosed with CF reported in the Region of Murcia until December 31, 2018. Seventy-six different variants were described being the most common c.1521_1523delCTT (p.Phe508del) in 58.3% of people and 37.0% of alleles. Sixty-seven percent of the patients were classified as high-risk genotype, which was associated with a lower percentage of FEV1 [OR: 3.4 (95%CI: 1.1, 10.8)], an increased risk of colonization by Pseudomonas aeruginosa and Achromobacter xylosoxidans [OR: 4.2 (95%CI: 1.3, 13.8) and 7.1 (95%CI: 1.1, 47.2), respectively] and the presence of pancreatic insufficiency [OR: 21.8 (95%CI: 7.9, 59.9)] as compared with those with mild variants.Conclusions: The Region of Murcia has one of the lowest allele frequencies of p.Phe508del described in Europe and high genetic heterogeneity, which could explain the high proportion of patients with mild disease. Furthermore, our results support the association between genotypes compound of two severe variants and the presence of pancreatic insufficiency, increased risk of respiratory infection, and serious lung damage.

Background:Cystic fibrosis (CF) is the most common multisystem, chronic, and life-threatening rare disease in the Caucasian population. Progressive loss of lung function remains the leading cause of death. However, improvementsin prognosis and survival have caused CF to go from being a lethal disease in childhood to becoming an increasingly frequent pathology in adults. In Spain, the factors that influence survival have not been determined. The objective of the study is to analyse survival and determine the factors associated with it in people with CF from a region in southeastern Spain based on information from a rare disease registry. Methods: A cross-sectional study was carried out in people with a confirmed diagnosis of CF up to December 31 2018, who were registered in the Rare Disease Information System of the Region of Murcia (SIERrm). The Kaplan‒Meier method and the log-rank test were used to estimate and compare survival curves. Predictors of survival were calculated using the Cox proportional hazards model. Results:Of the 192 patients registered in SIERrm with a confirmed diagnosis of CF, 39 patients died with a median age of 22 years (IQR: 15.0 - 33.0), of which 77% were classified within high-risk genotypes. The median survival age was 26.0 years (95% CI: 22.0 - 30.0),and the 10-year survival from diagnosis was 87.6%. In addition, high-risk genotype [HR: 5.8 (95% CI: 1.97 - 16.94)], pancreatic insufficiency [HR: 5.4 (95% CI: 1.24 - 23.48)], chronic colonization by Pseudomonas aeruginosa [HR: 6.8 (95% CI: 1.21 - 38.54)], the development of CF-related liver disease [HR: 5.0 (95% CI: 1.61 - 15.61)] and bone anomalies [HR: 6.4 (95% CI: 1.91 - 21.61)] were associated with decreased survival (p<0.05). Conclusions: In the Regionof Murcia, people with a high-risk genotype, pancreatic insufficiency, chronic colonization by Pseudomonas aeruginosa, and the development of CF-related bone and liver complications predict a higher risk of dying or being transplanted and therefore a decrease in survival. The use of population registries is useful for estimating survival and showing the factors associated with it, which is important for planning care needs and implementing personalized medicine that influences these factors.