title: Mutation analysis and haplotype correlation for 139 cystic fibrosis patients from the Nebraska Regional Cystic Fibrosis Center.
abstract: Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 individuals seen at The Nebraska Regional Cystic Fibrosis Center that included 139 CF patients, 206 parents, and 55 unaffected siblings to determine the frequency of the delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that included XV-2c, KM-19, pMP6d.9, and G2. Results from this study showed that the delta F508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the delta F508 deletion, 47 (34%) were heterozygous for the delta F508 deletion and an unknown mutation, and 18 (13%) carried two unknown mutations. Four additional mutations were also found in our population and included G542X (6%), G551D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that has previously been reported in several families was also present in our study. The most common haplotype associated with the delta F508 deletion in our CF patients was the E haplotype (CF Consortium B) while other mutations were associated with a variety of haplotypes.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.
authors.forename: M D
authors.initials: MD
authors.lastname: Traystman
authors.forename: N
authors.initials: N
authors.lastname: Schulte
authors.forename: J L
authors.initials: JL
authors.lastname: Colombo
authors.forename: P H
authors.initials: PH
authors.lastname: Sammut
authors.forename: P
authors.initials: P
authors.lastname: Reilly
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.forename: D
authors.initials: D
authors.lastname: Acquazzino
authors.forename: B
authors.initials: B
authors.lastname: Simanek
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: W J
authors.initials: WJ
authors.lastname: Kimberling
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009329:Nebraska; D012307:Risk Factors
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA