title: Cystic fibrosis mutation analysis: report from 22 U.K. regional genetics laboratories.
abstract: We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 22 laboratories in the United Kingdom. A total of 9,807 CF chromosomes have been analysed, demonstrating 56 different mutations so far observed and accounting for 86% of CF genes in the native Caucasian population of the United Kingdom. delta F508 is the most common at 75.3% of CF mutations (range 56.5-83.7%), followed by G551D (3.08%; range 0.71-7.60%), G542X (1.68%; range 0.85-3.66%), 621 + 1 (G > T) (0.93%; range 0.41-3.16%), 1717-1(G > A) (0.57%; range 0.17-1.14%), 1898 + 1)(G > A) (0.46%), R117H (0.46%), N1303K (0.46%), and R553X (0.46%). The data show a clear geographical variation in the distribution of some of the mutations, most notably a marked regional variation in the distribution of 621 + 1 (G > T) and 1989 + 1(G > A), which are both apparently more frequent in Wales. R560T and R117H appear to be more frequent in Ireland and Scotland, and G551D more frequent in Scotland. In summary, these data illustrate that the mutations present within a particular population need to be defined in order to provide meaningful carrier screening and testing for rare mutations in affected individuals. Furthermore, it is apparent that the ethnic origin of a patient, even within a small country such as the United Kingdom, should be taken into account.
authors.affiliation: Regional Molecular Genetics Laboratory, Royal Manchester Children's Hospital, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Schwarz
authors.forename: G M
authors.initials: GM
authors.lastname: Malone
authors.forename: A
authors.initials: A
authors.lastname: Haworth
authors.forename: J P
authors.initials: JP
authors.lastname: Cheadle
authors.forename: A L
authors.initials: AL
authors.lastname: Meredith
authors.forename: A
authors.initials: A
authors.lastname: Gardner
authors.forename: I H
authors.initials: IH
authors.lastname: Sawyer
authors.forename: M
authors.initials: M
authors.lastname: Connarty
authors.forename: N
authors.initials: N
authors.lastname: Dennis
authors.forename: A
authors.initials: A
authors.lastname: Seller
mesh_terms: D003550:Cystic Fibrosis / Q000453:epidemiology* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator