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
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...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-021-02049-z |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Panayiotis K. Yiallouros Andreas Μ. Matthaiou Pinelopi Anagnostopoulou Panayiotis Kouis Malgorzata Libik Tonia Adamidi Adonis Eleftheriou Artemios Demetriou Phivos Ioannou George A. Tanteles Constantina Costi Pavlos Fanis Milan Macek Vassos Neocleous Leonidas A. Phylactou |
| spellingShingle |
Panayiotis K. Yiallouros Andreas Μ. Matthaiou Pinelopi Anagnostopoulou Panayiotis Kouis Malgorzata Libik Tonia Adamidi Adonis Eleftheriou Artemios Demetriou Phivos Ioannou George A. Tanteles Constantina Costi Pavlos Fanis Milan Macek Vassos Neocleous Leonidas A. Phylactou 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 CFTR gene CFTR modulators Cystic fibrosis Next-generation sequencing Patient registry |
| author_facet |
Panayiotis K. Yiallouros Andreas Μ. Matthaiou Pinelopi Anagnostopoulou Panayiotis Kouis Malgorzata Libik Tonia Adamidi Adonis Eleftheriou Artemios Demetriou Phivos Ioannou George A. Tanteles Constantina Costi Pavlos Fanis Milan Macek Vassos Neocleous Leonidas A. Phylactou |
| author_sort |
Panayiotis K. Yiallouros |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
BMC |
| series |
Orphanet Journal of Rare Diseases |
| issn |
1750-1172 |
| publishDate |
2021-10-01 |
| description |
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. |
| topic |
CFTR gene CFTR modulators Cystic fibrosis Next-generation sequencing Patient registry |
| url |
https://doi.org/10.1186/s13023-021-02049-z |
| work_keys_str_mv |
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doaj-d498ad4172b8449e8db2bd2e48a0c43c2021-10-03T11:37:35ZengBMCOrphanet Journal of Rare Diseases1750-11722021-10-0116111210.1186/s13023-021-02049-zDemographic 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 registryPanayiotis K. Yiallouros0Andreas Μ. Matthaiou1Pinelopi Anagnostopoulou2Panayiotis Kouis3Malgorzata Libik4Tonia Adamidi5Adonis Eleftheriou6Artemios Demetriou7Phivos Ioannou8George A. Tanteles9Constantina Costi10Pavlos Fanis11Milan Macek12Vassos Neocleous13Leonidas A. Phylactou14Respiratory Physiology Laboratory, Medical School, Shacolas Educational Centre for Clinical Medicine, University of CyprusRespiratory Physiology Laboratory, Medical School, Shacolas Educational Centre for Clinical Medicine, University of CyprusRespiratory Physiology Laboratory, Medical School, Shacolas Educational Centre for Clinical Medicine, University of CyprusRespiratory Physiology Laboratory, Medical School, Shacolas Educational Centre for Clinical Medicine, University of CyprusDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and Motol University Hospital, Charles UniversityPulmonology Clinic, Nicosia General HospitalPulmonology Clinic, Paphos General HospitalPrivate PracticePaediatric Pulmonology Unit, Hospital ‘Archbishop Makarios III’Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and GeneticsDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and GeneticsDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and GeneticsDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and Motol University Hospital, Charles UniversityDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and GeneticsDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and GeneticsAbstract 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.https://doi.org/10.1186/s13023-021-02049-zCFTR geneCFTR modulatorsCystic fibrosisNext-generation sequencingPatient registry |