Demographic characteristics, clinical and laboratory features, and the distribution of pathogenic variants in the CFTR gene in the Cypriot cystic fibrosis (CF) population demonstrate the utility of a national CF patient registry

Orphanet Journal of Rare Diseases

George A. Tanteles¹  Malgorzata Libik²  Milan Macek²  Leonidas A. Phylactou³  Vassos Neocleous³  Pavlos Fanis³  Constantina Costi³  Phivos Ioannou⁴  Artemios Demetriou⁵  Tonia Adamidi⁶  Adonis Eleftheriou⁷  Panayiotis K. Yiallouros⁸  Pinelopi Anagnostopoulou⁸  Andreas Μ. Matthaiou⁸  Panayiotis Kouis⁸ 

[1] Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics;Department of Biology and Medical Genetics, 2nd Faculty of Medicine and Motol University Hospital, Charles University;Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics;Paediatric Pulmonology Unit, Hospital ‘Archbishop Makarios III’;Private Practice;Pulmonology Clinic, Nicosia General Hospital;Pulmonology Clinic, Paphos General Hospital;Respiratory Physiology Laboratory, Medical School, Shacolas Educational Centre for Clinical Medicine, University of Cyprus;

关键词: CFTR gene;    CFTR modulators;    Cystic fibrosis;    Next-generation sequencing;    Patient registry;   

DOI  :  10.1186/s13023-021-02049-z

来源: DOAJ

【 摘 要 】

Abstract Background Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients’ data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases. Results Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV1 z-scores were 0.2 ± 1.3 and − 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala. Conclusions CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.

【 授权许可】

Unknown