Clinical expression of cystic fibrosis in a large cohort of Italian siblings
| Autor: | Rita Padoan, Valeria Raia, Federica Zarrilli, Adriano Angioni, Cesare Braggion, Antonella Miriam Di Lullo, Serena Quattrucci, Donatello Salvatore, Giuseppe Castaldo, Mirella Collura, Vito Terlizzi, Natalia Cirilli, Manuela Seia, Rosaria Casciaro, Carla Colombo, Ausilia Elce, Vincenzina Lucidi, Vincenzo Carnovale, Marco Lucarelli, Roberto Buzzetti, Elisa Madarena, Arianna Bisogno, Lisa Termini |
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| Přispěvatelé: | Terlizzi, Vito, Lucarelli, Marco, Salvatore, Donatello, Angioni, Adriano, Bisogno, Arianna, Braggion, Cesare, Buzzetti, Roberto, Carnovale, Vincenzo, Casciaro, Rosaria, Castaldo, Giuseppe, Cirilli, Natalia, Collura, Mirella, Colombo, Carla, Di Lullo, Antonella Miriam, Elce, Ausilia, Lucidi, Vincenzina, Madarena, Elisa, Padoan, Rita, Quattrucci, Serena, Raia, Valeria, Seia, Manuela, Termini, Lisa, Zarrilli, Federica |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male liver diseases Oropharynx Gastroenterology Cystic fibrosis Severity of Illness Index cystic fibrosis Liver disease FEV1 0302 clinical medicine Forced Expiratory Volume Genotype CFTR Child siblings nasal polyps Middle Aged Phenotype exocrine pancreatic insufficiency Modifier genes Pseudomonas aeruginosa Pulmonary and Respiratory Medicine Italy meconium ileus Cohort diabetes mellitus genotype modifier genes phenotype pseudomonas aeruginosa carrier state cystic fibrosis transmembrane conductance regulator Female Research Article Adult medicine.medical_specialty Adolescent Genetic counseling Concordance 03 medical and health sciences Young Adult Diabetes mellitus Internal medicine medicine Humans lcsh:RC705-779 Modifier gene business.industry Infant Newborn Sputum Infant lcsh:Diseases of the respiratory system medicine.disease 030104 developmental biology 030228 respiratory system alpha 1-Antitrypsin Mutation business |
| Zdroj: | BMC Pulmonary Medicine BMC Pulmonary Medicine, Vol 18, Iss 1, Pp 1-8 (2018) |
| Popis: | Background A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. Methods We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. Results Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the “whole” CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. Conclusions Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain. Electronic supplementary material The online version of this article (10.1186/s12890-018-0766-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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