Next generation diagnostics of cystic fibrosis and<i>CFTR</i>-related disorders by targeted multiplex high-coverage resequencing of<i>CFTR</i>

Trujillano, Daniel; Ramos, María Dolores Burguete; González, Justo; Tornador, Cristian; Sotillo, Fernando; Escaramís, Geòrgia; Ossowski, Stephan; Armengol, Lluı́s; Casals, Teresa; Estivill, Xavier

doi:10.1136/jmedgenet-2013-101602

Cited by 40 publications

(44 citation statements)

References 28 publications

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“…Being aware of which mutations each patient carries also opens up new therapeutic options as more class specific drugs are developed 2,46 . As recent literature suggests 44,45 , sequencing has several advantages over panel tests and may be a cheaper and faster way to arrive at a diagnosis.…”

Section: The Way Forwardmentioning

confidence: 99%

“…This process would generate data that could resolve the patient's CF status, be useful in designing a genetic test with a higher mutation detection rate and determine if a patient may benefit from one of the class-specific drugs that have recently become available 2,46 . Alternatively, given recent data that suggests that pairing NGS with an appropriate bioinformatics pipeline could significantly reduce both the time and cost involved in CF diagnosis 44,45 , it may be time to begin switching to sequencing as the primary diagnostic method. This should have particular utility in diverse 13 populations such as are found in Africa and her Diaspora, which have suffered from the inherent European bias in the current genetic tests.…”

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confidence: 99%

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Cystic Fibrosis in the African Diaspora

Stewart

Pepper

2017

Annals ATS

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Identifying mutations that cause cystic fibrosis (CF) is important for making an early, unambiguous diagnosis, which in turn is linked to better health and a greater life expectancy. In patients of African descent, a molecular diagnosis is often confounded by the fact that the majority of investigations undertaken to identify causative mutations have been conducted on European populations, and CF-causing mutations tend to be population specific. We undertook a survey of published data with the aim of identifying causative CF mutations in patients of African descent in the Americas. We found that 1,584 chromosomes had been tested in only six countries of which 876 alleles (55.3%) still remained unidentified. There were 59 mutations identified -41 of which have been shown to cause CF, 17 have no associated functional studies and one (R117H) is of varying clinical consequence. The most common mutations identified in the Diaspora were ΔF508 (29.4%; identified in America, Colombia, Brazil and Venezuela), 3120+1G>A (8.4%; identified in Brazil, America and Colombia), G85E (3.8% identified in Brazil), 1811+1.6kbA>G (3.7% identified in Colombia), and 1342-1G>C (3.1% identified in America). The majority of the mutations identified (81.4%) have been described in just one country. Our findings indicate that there is a need to fully characterise the spectrum of CF mutations in the Diaspora in order to improve diagnostic accuracy for these patients and facilitate treatment.2

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Section: The Way Forwardmentioning

confidence: 99%

mentioning

confidence: 99%

Cystic Fibrosis in the African Diaspora

Stewart

Pepper

2017

Annals ATS

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“…With the upcoming introduction of NGS, the number of identified VUs will be greatly increased (Abou Tayoun et al, 2013, Trujillano et al, 2013. The labelling of these VUs, as diseasecausing or as neutral (Group C) mutations, will be challenging.…”

Section: Assigning Cftr Mutations To Cf Patients: a Methodological Pementioning

confidence: 99%

Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies

Fanen

Wohlhuter-Haddad

Hinzpeter

2014

The International Journal of Biochemistry & Cell Biology

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Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an epithelial anion channel. This review presents the current CFTR mutation classifications according to their clinical consequences and to their effect on the structure and function of the CFTR channel. How these classifications are essential in the establishment of mutation-targeted therapeutic strategies is then discussed. The future of CFTR-targeted treatment lies in combinatory therapies that will enable CF patients to receive a customized treatment.3

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“…No obstante, si analizamos las bajas coberturas que estos kits presentan para la población sudamericana, existe una clara necesidad de ampliar herramientas de secuenciamiento de ADN de próxima generación (en inglés: Next Generation Sequencing) (23) para aumentar las tasas de detección. Por otra parte, las herramientas de secuenciación directa del CFTR y la búsqueda de reordenamientos genómicos permitirán detectar posibles mutaciones prevalentes a nivel regional y mutaciones raras (privados) que no se encuentran con las pruebas de mutaciones específicas propuestas por los kits de ARMS-PCR (24,25) .…”

Section: Alelos Mutados N = 72unclassified