Recommendations for the classification of diseases as CFTR-related disorders

Abstract

Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

“…Normally, effective mucociliary transport is facilitated by sufficient hydration of the airway surface liquid (ASL); an important periciliary and mucus layer that lines the airway tract [30,31]. ASL hydration is achieved through establishment of an osmotic gradient by a predominant efflux of chloride ions through CFTR channels, coupled with a moderate influx of sodium ions through epithelial known to affect mRNA production, although to a lesser degree than CF-causing CFTR mutations [23]. CBAVD: congenital bilateral absence of vas deferens.…”

Assessing the Disease-Liability of Mutations in CFTR

“…However, it was important to distinguish patients who do not meet the diagnosis criteria for CF but for whom there was evidence of CFTR dysfunction and finally, recently, the term CFTR-related disorders (CFTR-RD) has been accepted by the community (Bombieri et al 2011). A CFTR-RD is defined as a clinical entity associated with CFTR dysfunction that does not fulfill the diagnostic criteria for CF.…”

“…The two most common CFTR-RD alleles are the IVS8-5T, a poly T tract in intron 8 of the CFTR, and the R117H associated with the 7T tract (Chilló n et al 1995). The IVS8-5T allele, which is present on at least 5% of "normal CFTR genes," is the most frequent CFTR-RD allele worldwide (Bombieri et al 2011). Its frequency in CBAVD males is 5-8 times higher than in the general population (Chilló n et al 1995;Zielenski et al 1995).…”

Einführung des deutschlandweiten Neugeborenenscreenings für Mukoviszidose

“…1 : 3.300-1 : 5.800 die häufigste angeborene Stoffwechselerkrankung in Deutschland [6][7][8] weitere Symptome einer Mukoviszidose zeigt. Patienten mit dieser Form haben eine sogenannte CFTR-related disorder (CFTR-RD), die von der klassischen Mukoviszidose abgegrenzt wird [14].…”