Format

Send to

Choose Destination
BMC Pulm Med. 2018 Dec 22;18(1):196. doi: 10.1186/s12890-018-0766-6.

Clinical expression of cystic fibrosis in a large cohort of Italian siblings.

Author information

1
Dipartimento di Pediatria, Centro Regionale Toscano per la Fibrosi Cistica, Azienda Ospedaliero-Universitaria Meyer, Viale Gaetano Pieraccini 24, 50139, Florence, Italy. terlizzivito@libero.it.
2
Dipartimento di Biotecnologie Cellulari ed Ematologia, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza Università e Policlinico Umberto I, Rome, Italy.
3
Centro Regionale Fibrosi Cistica, Centro Pediatrico Bambino Gesù Basilicata, AOR San Carlo, Potenza, Italy.
4
Laboratorio di Genetica Medica, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
5
Centro Regionale Fibrosi Cistica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
6
Dipartimento di Pediatria, Centro Regionale Toscano per la Fibrosi Cistica, Azienda Ospedaliero-Universitaria Meyer, Viale Gaetano Pieraccini 24, 50139, Florence, Italy.
7
Freelance Epidemiologist, Bergamo, Italy.
8
Centro Regionale Fibrosi Cistica Adulti, Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, Naples, Italy.
9
Centro Regionale Fibrosi Cistica, U.O.C. Pneumologia, IRCCS G. Gaslini, Genua, Italy.
10
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
11
CEINGE-Biotecnologie avanzate, Naples, Italy.
12
Centro Regionale Fibrosi Cistica, Dipartimento Materno-Infantile, Ospedali Riuniti Ancona, Ancona, Italy.
13
CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico, Palermo, Italy.
14
Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologica, Università di Napoli Federico II, Naples, Italy.
15
Università Telematica Pegaso, Naples, Italy.
16
Unità Regionale di Fibrosi Cistica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
17
Centro Regionale Fibrosi Cistica, Ospedale Giovanni Paolo II, Lamezia, Italy.
18
Centro Regionale di supporto Fibrosi Cistica, Dipartimento di Pediatria, Università di Brescia, AO Spedali Civili, Brescia, Italy.
19
Centro Fibrosi Cistica Regione Lazio, Dipartimento di Pediatria e Neuropsichiatria Infantile, Sapienza Università-Policlinico Umberto I, Rome, Italy.
20
Centro Regionale Fibrosi Cistica, Sezione Pediatrica, Dipartimento di Scienze Mediche Traslazionali, Università di Napoli Federico II, Naples, Italy.
21
Laboratorio di Genetica Medica, Fondazione IRCCS Policlinico Ca' Granda Ospedale, Milan, Italy.
22
Ospedale dei Bambini G. Di Cristina, Centro Regionale Fibrosi Cistica, Palermo, Italy.
23
Dipartimento di Bioscienze e Territorio, Università del Molise, Isernia, Italy.

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.

KEYWORDS:

CFTR; FEV1; Genotype; Modifier genes; Phenotype; Pseudomonas aeruginosa

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center