Cystic fibrosis mutation analysis: Report from 22 U.K. regional genetics laboratories

Schwarz, Martin; Malone, Geraldine; Haworth, Andrea; Cheadle, Jeremy P.; Meredith, A L; Gardner, Anne; Sawyer, Ian; Connarty, M.; Dennis, N R; Seller, A; Harris, Ann; Taylor, Rohan; Dear, Simon; Middleton‐Price, Helen; McMahon, Cathie; Mayall, Ed; McMahon, Rob; Barton, D. E.; Giles, M.D.; Lindley, Victoria; Plaha, Davinder S.; Price, Susan; Sharif, Abid; Cross, Gareth; Dalton, Ann; Taylor, Graham W.; Wallace, Andrew; Tassabehji, Mayada; Whittaker, Joanne; Butler, Rachel; Curtis, Ann; Pinkett, Ros; Gilfillan, Annette; Brock, D. J. H.; Higgins, Gerard; Lanyon, G. W.; Miedzybrodzka, Zosia; Davidson, M. J.; Graham, Colin A.; Hill, Alison

doi:10.1002/humu.1380060406

Cited by 36 publications

(22 citation statements)

References 31 publications

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“…Although as a whole France fits into the European trend of an increasing frequency of ΔF508 from the Southeast to the Northwest (table 2), there are significant regional variations within France not following this trend. The same situation has been observed in Italy and the United Kingdom [10, 11]. The highest frequencies (>72%) are found in four regions, the lowest (<65%) in eight regions.…”

Section: Resultssupporting

confidence: 52%

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Cystic Fibrosis Mutations: Report from the French Registry

et al. 1999

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Data from 2,666 patients with cystic fibrosis (CF) born in France, submitted during the period of 1992–1996 to the French registry for CF, were used to describe the different mutations, their frequency and their regional distribution. A total of 5,332 CF chromosomes have been analyzed, demonstrating 229 different mutations and accounting for 87% of CF genes in the French population. ΔF508 is the most common mutation at 67.9% of CF mutations, followed by G542X (2.5%), N1303K (2.0%), 1717–1G→A (1.2%), R553X (0.8%) and G551D (0.7%). The data show a clear geographical variation in the distribution of many of the mutations. Given the geographical heterogeneity of these mutations, carrier screening does not appear to be feasible in most French regions.

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Section: Resultssupporting

confidence: 52%

“…In these populations, their frequencies are higher than those observed in France. These mutations are rather common in Germany and the United Kingdom [11, 15]. G542X and N1303K are the second most frequent mutations in 12 and 3 of the French regions, respectively.…”

Section: Resultsmentioning

confidence: 99%

Cystic Fibrosis Mutations: Report from the French Registry

et al. 1999

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“…In addition, transgenic animals expressing λN-DD, a guide oligonucleotide, or both could be generated to create useful models for human disease. Furthermore, recessive diseases like cystic fibrosis are often caused by alleles that carry different mutations, one of which could be corrected by editing (24,36). At present this technique is limited to those mutations that can be corrected by recoding an A to an I; however, in principle the same approach could probably be extended to cytidine deaminases to convert C to U.…”

Section: Discussionmentioning

confidence: 99%

Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing

Montiel-González

Vallecillo-Viejo

Yudowski

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

188

198

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Adenosine deaminases that act on RNA are a conserved family of enzymes that catalyze a natural process of site-directed mutagenesis. Biochemically, they convert adenosine to inosine, a nucleotide that is read as guanosine during translation; thus when editing occurs in mRNAs, codons can be recoded and the changes can alter protein function. By removing the endogenous targeting domains from human adenosine deaminase that acts on RNA 2 and replacing them with an antisense RNA oligonucleotide, we have engineered a recombinant enzyme that can be directed to edit anywhere along the RNA registry. Here we demonstrate that this enzyme can efficiently and selectively edit a single adenosine. As proof of principle in vitro, we correct a premature termination codon in mRNAs encoding the cystic fibrosis transmembrane conductance regulator anion channel. In Xenopus oocytes, we show that a genetically encoded version of our editase can correct cystic fibrosis transmembrane conductance regulator mRNA, restore fulllength protein, and reestablish functional chloride currents across the plasma membrane. Finally, in a human cell line, we show that a genetically encoded version of our editase and guide RNA can correct a nonfunctional version of enhanced green fluorescent protein, which contains a premature termination codon. This technology should spearhead powerful approaches to correcting a wide variety of genetic mutations and fine-tuning protein function through targeted nucleotide deamination.

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“…Schwarz et al studied the distribution and frequency of Caucasian UK CFTR mutations in 1995 7 and listed 20 of the commonest mutations. Nineteen of these mutations feature in the commonest UK Caucasian 20 mutations listed in Table 4.…”

Section: Cftr Mutations In Caucasiansmentioning

confidence: 99%

“…Northern Ireland has a much greater proportion of Other/Other CF patients (where neither mutation is DF508) and although there is a higher incidence of CF in Northern Ireland (one in 1850), the population frequency of DF508 is similar to other regions of the UK. 7 CFTR mutations in the Non-Caucasian population Cystic Fibrosis is being increasingly diagnosed in the nonCaucasian populations, and the range of presenting features is similar between Caucasian and ISC groups ( Table 1). The genotypes of non-Caucasian patients often contain individual or family specific mutations along with mutations more commonly found in Caucasians due to admixture of the populations.…”

Section: Cftr Mutations In Caucasiansmentioning

confidence: 99%