Spatial patterns of cystic fibrosis mutation spectra in European populations

Lao, Oscar; Andrés, Aida M.; Mateu, Eva; Bertranpetit, Jaume; Calafell, Francesc

doi:10.1038/sj.ejhg.5200970

Cited by 41 publications

(26 citation statements)

References 46 publications

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“…The remaining third of alleles are substantially heterogeneous, with fewer than 20 mutations occurring at a worldwide frequency of more than 0.1% [4,11]. Some mutations can reach a higher frequency in certain populations, due to a founder effect in religious, ethnic or geographical isolates [12,13] (Tables 1 and 2). …”

Section: Distribution Of Mutationsmentioning

confidence: 99%

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Castellani

Cuppens

Maçek

et al. 2008

Journal of Cystic Fibrosis

530

455

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It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.

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Section: Distribution Of Mutationsmentioning

confidence: 99%

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Castellani

Cuppens

Maçek

et al. 2008

Journal of Cystic Fibrosis

530

455

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show abstract

“…This important population admixing could explain the lower frequency of CF among neonates but cannot explain the higher allelic heterogeneity in this region. According to a recent study, the major factor that contributed to the CF mutation diversity is the size of ancestral population [3]. It is believed that at the postglaciation phase and later during the Neolithics, population expansion has started earlier, and then expanded much faster and more extensively along the Mediterranean shores than in northern parts of Europe, presumably due to more favourable living conditions [3].…”

Section: Increased Diversity Of Cftr Mutations In Languedocroussillonmentioning

confidence: 99%

“…The accurate knowledge of CFTR mutations has obvious interest in clinical testing, as it improves CF prevention programmes of neonatal screening, heterozygote screening in partners of CF patients or partners of carriers, and CF diagnosis in prenatal or postnatal circumstances. Reporting updated data is also crucial in population genetics, as most papers on CFTR mutation frequencies and history are compiled from the literature [2,3].…”

Section: Introductionmentioning

confidence: 99%

High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France

Georges

Guittard

Altiéri

et al. 2004

Journal of Cystic Fibrosis

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In this report, we present updated spectrum and frequency of mutations of the CFTR gene that are responsible for cystic fibrosis (CF) in Languedoc-Roussillon (L-R), the southwestern part of France. A total of 75 different mutations were identified by DGGE in 215 families, accounting for 97.6% of CF genes and generating 88 different mutational genotypes. The frequency of p.F508del was 60.23% in L-R versus 67.18% in the whole country and only five other mutations (p.G542X, p.N1303K, p.R334W, c.1717-1G>A, c.711+1G>T) had a frequency higher than 1%. The mutations were scattered over 20 exons or their border. This sample representing only 5.7% of French CF patients contributed to 24% of CFTR mutations reported in France. This is one of the highest molecular allelic heterogeneity reported so far in CF. We also present the result of a neonatal screening program based on a two-tiered approach "IRT/20 mutations/IRT" analysis on blood spots, implemented in France with the aim to improve survival and quality of life of patients diagnosed before clinical onset. This 18-month pilot project showed an unexpected low incidence of CF (1/8885) in South of France, with only six CF children detected among 43,489 neonates born in L-R, and 13 among 125,339 neonates born in Provence-Alpes-Côte-d'Azur (PACA).

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“…The most common CF mutation is F508del (two-thirds of all CF mutations) with an incidence decreasing from northwest Europe to southeast Europe (5)(6)(7)(8)(9)(10). Although in a worldwide context most CFTR mutations do not have a frequency Ͼ0.1%, some may still be common in various ethnic, religious, or geographically isolated groups (1,2,(11)(12)(13).…”

confidence: 99%

A Novel Approach to CFTR Mutation Testing by Pyrosequencing-Based Assay Panels Adapted to Ethnicities

Bickmann¹,

Kamin

Wiebel

et al. 2009

Clinical Chemistry

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Background: Cystic fibrosis (CF) is a common autosomal recessive genetic disorder caused by a variety of sequence alterations in the CFTR gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)]. Because the relative prevalence of mutations strongly depends on the ethnic background, first-level testing of CF as defined by recent consensus recommendations ought to be adaptable to the ethnicity of patients. Methods: We therefore developed and implemented a diagnostic approach to first-level testing for CF based on published mutation frequencies and Pyrosequencing (PSQ) technology that we complemented with standard procedures of mutation detection at the second level. Results: The current test system of PSQ assays for 46 target CF mutations [including CFTRdele2,3 (21 kb) and 1342-6 (T)n (5T/7T/9T)] permits recombinations of single assays to optimize sensitivities for certain ethnicities. By easy expansion of the original mutation panel, the first-level test sensitivities with other ethnic groups would be increased, provided that the mutation frequencies are known. The test was validated with our local, ethnically mixed, but mainly German population (155 patients). The mutation-detection rate for the 92 patients whose CF was confirmed by the sweat test was 89.0% for the patients of German descent (73 of the 92 patients) and 73.7% for the patients of any other origin (19 of the 92 patients). Ethnicity-adapted testing panels for our foreign CF patients would increase the sensitivities for the respective groups by approximately 5%. Conclusions: PSQ-based genotyping is a reliable, convenient, highly flexible, and inexpensive alternative to conventional methods for first-level testing of CFTR, facilitating flexible adaptation of the analyzed mutation panel to any local ethnic group.

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Spatial patterns of cystic fibrosis mutation spectra in European populations

Cited by 41 publications

References 46 publications

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France

A Novel Approach to CFTR Mutation Testing by Pyrosequencing-Based Assay Panels Adapted to Ethnicities

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