Analysis of the genotypic profile and its relationship with the clinical manifestations in people with cystic fibrosis: study from a rare disease registry

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 FEV(1) (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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02373-y.