Two novel mutations in a cystic fibrosis patient of Chinese origin

Cystic fibrosis is rare in non-Caucasian populations, and in such populatio ns little is known about the spectrum of mutations and polymorphisms in the CFTR gene. We studied a 23-year-old patient of Chinese ethnicity with swea t chloride values of 104 mM/l, pancreatic sufficiency, an FEV1 60% of norma l, sputum cultures positive for Staphylococcus aureus and Burkholderia cepa cia, and a history of allergic bronchopulmonary aspergillosis. Genetic scre ening for 31 common CFTR mutations was negative, leading us to search for u nknown mutations using single-strand conformation polymorphism and heterodu plex analysis (SSCP/HA). Two novel mutations were detected. In exon 4, a de letion of 8 bp (451-458, Delta GCTTCCTA) causes a frameshift and immediatel y creates a stop codon. In exon 16, mutation 3041G-->A causes the missense change G970D. Functional analysis using an isotopic flux assay indicated th at the G970D mutation retains partial function; western blotting indicated that the protein is glycosylated. The patient is heterozygous for the commo n polymorphisms (2694T/G) in exon 14a and (GATT)(6/7) in intron 6a, indicat ing that these variants arose in ancestors common to Caucasians and Chinese .