During the course of screening the DNA of cystic fibrosis patients for the presence of unknown mutations using the single-strand conformational polymorphism (SSCP) technique in a modified nonisotopic form on the Pharmacia Phast system as proposed by Dockhorn-Dworniczak et al. (1991), the DNA of a young patient heterozygous for AF508 showed an aberrant band pattern in exon 4.
Exon 4 was sequenced by means of an AB1 automatic sequencer 373A using the Dyedeoxy Terminator Sequencing Kit and a Taq Cycling protocol.
A transition from C to T in position 455 (numbered according to , was found that could be confirmed by identifying the corresponding G-to-A transition in the antisense strand. This base exchange leads to stibsritution of serine in position 108 of the CFTR protein by phenylalanine. According to the rules given by , the mutation should be designated S108F.
The patient is a young man who was first diagnosed as having cystic fihrosis at the age of 19. His length is 180 cm and his weight 70 kg. He has a Shwachman clinical score of 75 and a FEV,% of 80%. The chest radiography shows bronchiectatic changes. He is pancreas sufficient and there are no signs of Psedomonas colonization up to now. Sweat chloride levels are elevated (120 mmol/L).
The propositus has inherited the S108F allele from his mother as could be shown by SSCP screening and suhsequent sequencing. His AF508 allele as well as that of his brother come from the paternal line.