CFTR and cystic fibrosis: Similarly, the CFTR genotype of the evolved patients was not particularly suggestive of the clinical course, i.e., four of the eight patients evolved to CFTR-RD had a severe variant in trans with the D1152H variant, that has a very heterogeneous clinical impact [22], while both the cases of CF-SPID evolved to CF had a severe variant in trans with the [5 T;TG12] complex allele, confirming in turn the heterogeneous clinical impact of such complex allele that was found, in trans with a severe variant either in asymptomatic subjects, in CFTR-RD and in CF patients [5].