Analysis Of The Genotypic Profile And Its Relationship With The Clinical Manifestations In People With Cystic Fibrosis: Study From A Registry Of Rare Diseases.

Abstract 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.