THE RARE CFTR MUTATION Y301C

CFTR is a well-known gene, of which mutations have been extensively characterized. However, some very rare mutations of this gene are still missing a clear understanding of their real clinical significance. This is the case, for instance, of the mutation c.902A>G (p.Y301C), detectable in exon 8. This is a very rare mutation, with limited data about its phenotypic effect. The mutation was firstly reported by Constantinou-Deltas CD et al. in a study on the Cyprus population (Hum Mutat 1992; 1:503-5). Another report about this mutation is by Castellani C et al (PMID: 9915972): the authors found this mutation also in compound heterozygosity with a second mutation in neonates with normal sweat chloride test but with hypertrypsinemia, stating that the diagnosis of cystic fibrosis in these patients remained a moot point. According to the Italian Foundation for Research on Cystic Fibrosis (http://www.fibrosicisticaricerca.it/Fibrosi-Cistica/Domande-e-risposte/Mutazione-Y301C), this mutation has been described in patients with altered sweat test who showed atypical signs of the disease, like respiratory and pancreatic symptoms. It is very important to note that the phenotypic effect of any CFTR mutation is depending on the type of the mutation itself (severe or mild) and on the genotypic combination possibilities between severe and mild mutations. Thus, when this mutation is found in an unaffected person, it may be appropriate to define this individual as being carrier of a CFTR pathogenic mutation of which phenotypic effect remains poorly defined.