title: Novel Cystic Fibrosis mutation L1093P: functional analysis and possible Native American origin.
abstract: A novel mutation was detected using single-strand conformation polymorphism and heteroduplex analysis in a cystic fibrosis subject of mixed ancestry. Mutation 3410T-->C in exon 17b caused the novel missense mutation L1093P; the other chromosome has mutation N1303K. The 31-year-old subject is pancreatic insufficient, had an FEV(1) score that was 33% of normal prior to a heart/lung transplant, and sweat chloride values of 116 and 95 mM when tested at ages 1 and 11. Functional analysis using forskolin-stimulated efflux of (125)I in HEK cells transfected with an ABCC7 construct harboring the L1093P mutation confirmed that cAMP-mediated anion efflux was abnormal, but some function was preserved. Analysis of parental DNA established that N1303K was of English origin, while L1093P was of Greek, Irish or Native American (Cherokee) origin. Given the intensive screening for CF mutations in European populations, we hypothesize that L1093P is of Native American origin. Hum Mutat 15:208, 2000.
authors.affiliation: Cystic Fibrosis Research Laboratory, Stanford University, Stanford, CA 94305-2130, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yee
authors.forename: C
authors.initials: C
authors.lastname: Robinson
authors.forename: G
authors.initials: G
authors.lastname: Hurlock
authors.forename: R B
authors.initials: RB
authors.lastname: Moss
authors.forename: J J
authors.initials: JJ
authors.lastname: Wine
mesh_terms: D000328:Adult; D000838:Anions / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014162:Transfection
chemical_list: D000838:Anions; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin