Abstract
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.
| Original language | English |
|---|---|
| Article number | 196 |
| Journal | BMC Pulmonary Medicine |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 22 2018 |
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Keywords
- CFTR
- FEV
- Genotype
- Modifier genes
- Phenotype
- Pseudomonas aeruginosa
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Clinical expression of cystic fibrosis in a large cohort of Italian siblings. / 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.
In: BMC Pulmonary Medicine, Vol. 18, No. 1, 196, 22.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical expression of cystic fibrosis in a large cohort of Italian siblings
AU - Terlizzi, Vito
AU - Lucarelli, Marco
AU - Salvatore, Donatello
AU - Angioni, Adriano
AU - Bisogno, Arianna
AU - Braggion, Cesare
AU - Buzzetti, Roberto
AU - Carnovale, Vincenzo
AU - Casciaro, Rosaria
AU - Castaldo, Giuseppe
AU - Cirilli, Natalia
AU - Collura, Mirella
AU - Colombo, Carla
AU - Di Lullo, Antonella Miriam
AU - Elce, Ausilia
AU - Lucidi, Vincenzina
AU - Madarena, Elisa
AU - Padoan, Rita
AU - Quattrucci, Serena
AU - Raia, Valeria
AU - Seia, Manuela
AU - Termini, Lisa
AU - Zarrilli, Federica
PY - 2018/12/22
Y1 - 2018/12/22
N2 - 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.
AB - 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.
KW - CFTR
KW - FEV
KW - Genotype
KW - Modifier genes
KW - Phenotype
KW - Pseudomonas aeruginosa
UR - http://www.scopus.com/inward/record.url?scp=85058920504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058920504&partnerID=8YFLogxK
U2 - 10.1186/s12890-018-0766-6
DO - 10.1186/s12890-018-0766-6
M3 - Article
C2 - 30577776
AN - SCOPUS:85058920504
VL - 18
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
SN - 1471-2466
IS - 1
M1 - 196
ER -