Two novel mutations in a cystic fibrosis patient of Chinese origin.
Cystic fibrosis is rare in non-Caucasian populations, and in such populations 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 sweat chloride values of 104 mM/l, pancreatic sufficiency, an FEV1 60% of normal, sputum cultures positive for Staphylococcus aureus and Burkholderia cepacia, and a history of allergic bronchopulmonary aspergillosis. Genetic screening for 31 common CFTR mutations was negative, leading us to search for unknown mutations using single-strand conformation polymorphism and heteroduplex analysis (SSCP/HA). Two novel mutations were detected. In exon 4, a deletion of 8 bp (451458, deltaGCTTCCTA) causes a frameshift and immediately creates a stop codon. In exon 16, mutation 3041G-->A causes the missense change G970D. Functional analysis using an isotopic flux assay indicated that the G970D mutation retains partial function; western blotting indicated that the protein is glycosylated. The patient is heterozygous for the common polymorphisms (2694T/G) in exon 14a and (GATT)6/7 in intron 6a, indicating that these variants arose in ancestors common to Caucasians and Chinese.
Wagner
J A
JA
Department of Molecular Pharmacology, Stanford University School of Medicine, CA 94305-5332, USA.
Vassilakis
A
A
Yee
K
K
Li
M
M
Hurlock
G
G
Krouse
M E
ME
Moss
R B
RB
Wine
J J
JJ
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002681:China / Q000208:ethnology; D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational