Two novel mutations in the transmembrane domains of the CFTR gene in subjects of Sardinian descent

Cystic Fibrosis (CF) is an autosomal recessive disorder characterized by a severe generalized exocrinopathy. The coding regions of the responsible gene, named CFTR, have been cloned and sequenced. In the CFTR gene more than 300 different mutations, including missense, nonsense and frameshift mutations, have been so far identified (CF Genetic Analysis Consortium, personal communication), the most common being a deletion of a phenylalanine residue at position 508 of the first Nucleotide Binding Fold (NBF1). In molecular screening for CF defects in Sardinians, carried out by DGGE analysis of exons 4-7-10-11-14a-15-17b-20-21, we identified two novel mutations: a C arrow right T transversion at nt 1145 (T338I) and a C arrow right A transversion at nt 2867 (S912X). The C arrow right T transversion produces a missense mutation Thr arrow right Ile at amino acid 338 in exon 7, which codes for the first transmembrane domain. The C arrow right A transversion leads to a nonsense mutation Ser arrow right Stop at amino acid 912 in exon 15, which codes for the second transmembrane domain.