Journal ArticleDOI
Cystic fibrosis mutation analysis: Report from 22 U.K. regional genetics laboratories
Martin Schwarz,Geraldine Malone,Andrea Haworth,Jeremy Peter Cheadle,A. Linda Meredith,Anne Gardner,I. Hilary Sawyer,Margaret Connarty,Nick Dennis,Anneke Seller,Ann Harris,Ann Harris,Rohan Taylor,Simon Dear,Helen Middleton-Price,Cathie McMahon,Ed Mayall,Robert C. McMahon,David E. Barton,Martin Giles,Victoria Lindley,Davinder S. Plaha,Susan Price,Abid Sharif,Gareth S. Cross,Ann Dalton,Graham R. Taylor,Andrew L. Wallace,Mayada Tassabehji,Joanne Whittaker,Rachel Butler,Ann Curtis,Ros Pinkett,Annette Gilfillan,David J. H. Brock,G. Scott Higgins,George W. Lanyon,Zosia Miedzybrodzka,Mark Davidson,Colin A. Graham,Alison J. M. Hill +40 more
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TLDR
The 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 and 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.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. ΔF508 is the most common at 753% 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. © 1995 Wiley-Liss, Inc.read more
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Journal ArticleDOI
Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening.
TL;DR: From comprehensive assessment of data, it is offered recommendations that multiple CFTR alleles should eventually be included to increase the sensitivity of newborn screening programs employing two‐tier testing with trypsinogen and DNA analysis.
Journal ArticleDOI
Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.
Eric W.F.W. Alton,M Stern,Raymond Farley,Adam Jaffe,Sharon Chadwick,J. Phillips,Jane C. Davies,Stephen N. Smith,JE Browning,Michael G. Davies,Margaret E. Hodson,Stephen R. Durham,D. Li,Peter K. Jeffery,M. Scallan,RP Balfour,Simon J. Eastman,Seng H. Cheng,Alan E. Smith,D. P. Meeker,Duncan M. Geddes +20 more
TL;DR: The safety and efficacy of cationic-lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis was studied in a double-blind placebo-controlled trial.
Journal ArticleDOI
Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations
TL;DR: Overall 55 mutations are common in one or several countries or regions of Europe and 217 mutations are rare with relative frequencies of lower than 1% in any of these regions and countries.
Journal ArticleDOI
Neonatal screening for inborn errors of metabolism: cost, yield and outcome
TL;DR: The majority of economic evaluations failed to incorporate the health benefits from screening, and therefore failed to address the value of the information which the screening programmes provided to parents.
Journal ArticleDOI
Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France.
Mireille Claustres,C. Guittard,Dominique Bozon,Francoise Chevalier,C. Verlingue,Claude Férec,Emanuelle Girodon,Cécile Cazeneuve,Thierry Bienvenu,Guy Lalau,Viviane Dumur,Delphine Feldmann,Eric Bieth,Martine Blayau,Christine Clavel,Isabelle Creveaux,M.-C. Malinge,Nicole Monnier,Perrine Malzac,Hervé Mittre,Jean-Claude Chomel,Jean-Paul Bonnefont,Albert Iron,Michèle Chery,Marie des Georges +24 more
TL;DR: The distribution of genotypes, classified according to the expected effect of their mutations on CFTR protein, clearly differed between both populations, and showed a clear geographical and/or ethnic variation in the distribution of the most common CF mutations.
References
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Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Journal ArticleDOI
Identification of the cystic fibrosis gene: genetic analysis.
Batsheva Kerem,Johanna M. Rommens,Janet A. Buchanan,Danuta Markiewicz,Tara K. Cox,Aravinda Chakravarti,Manuel Buchwald,Lap-Chee Tsui +7 more
TL;DR: Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations.
Journal ArticleDOI
Identification of the cystic fibrosis gene: Chromosome walking and jumping
Johanna M. Rommens,Michael C. Iannuzzi,Batsheva Kerem,Mitchell L. Drumm,Georg Melmer,Michael Dean,Richard Rozmahel,Jeffery L. Cole,Dara Kennedy,Noriko Hidaka,Martha Zsiga,Manuel Buchwald,John R. Riordan,Lap-Chee Tsui,Francis S. Collins +14 more
TL;DR: Several transcribed sequences and conserved segments were identified in this cloned region and one corresponds to the cystic fibrosis gene and spans approximately 250,000 base pairs of genomic DNA.
Journal ArticleDOI
Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.
Batsheva Kerem,Julian Zielenski,Danuta Markiewicz,Dominique Bozon,E Gazit,J Yahav,Dara Kennedy,John R. Riordan,Francis S. Collins,Johanna M. Rommens +9 more
TL;DR: The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward.
Journal ArticleDOI
A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations
W. Edward Highsmith,Lauranell H. Burch,Zhaoqing Zhou,John C. Olsen,Thomas E. Boat,Alexander Spock,Jack D. Gorvoy,Lynne M. Quittell,Kenneth J. Friedman,Lawrence M. Silverman,Richard C. Boucher,Michael R. Knowles +11 more
TL;DR: A point mutation in intron 19 of CFTR and abnormal epithelial function in patients who have cystic fibrosis-like lung disease but normal sweat chloride values is identified, indicating that this syndrome is a form of cystic Fibrosis.