CFTR protein analysis of splice site mutation 2789+5 G-A

Barneveld, Andrea van; Stanke, Frauke; Claass, Andreas; Ballmann, Manfred; Tümmler, Burkhard

doi:10.1016/j.jcf.2007.07.007

Cited by 5 publications

(1 citation statement)

References 15 publications

(33 reference statements)

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“…The subject thus qualified for treatment with ELX/TEZ/IVA and then showed strong improvements in lung function, lung morphology and sweat chloride ( Aalbers et al, 2022 ). On the other hand, the rather common splice mutation c.2657 + 5G>A is a class V mutation that is known to confer some residual wild-type CFTR activity ( Highsmith et al, 1997 ; van Barneveld et al, 2008 ). However, ELX/TEZ/IVA therapy of pwCF with one or two c.2657 + 5G>A mutations led to only marginal or no clinical improvement ( Table 3 ) ( Burgel et al, 2023 ).…”

Section: Exposure Of Elx/tez/iva To Rare Cftr Geno...mentioning

confidence: 99%

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Tümmler

2023

Front. Pharmacol.

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Triple combination therapy with the CFTR modulators elexacaftor (ELX), tezacaftor (TEZ) and ivacaftor (IVA) has been qualified as a game changer in cystic fibrosis (CF). We provide an overview of the body of literature on ELX/TEZ/IVA published between November 2019 and February 2023 after approval by the regulators. Recombinant ELX/TEZ/IVA-bound Phe508del CFTR exhibits a wild type conformation in vitro, but in patient’s tissue a CFTR glyoisoform is synthesized that is distinct from the wild type and Phe508del isoforms. ELX/TEZ/IVA therapy improved the quality of life of people with CF in the real-life setting irrespective of their anthropometry and lung function at baseline. ELX/TEZ/IVA improved sinonasal and abdominal disease, lung function and morphology, airway microbiology and the basic defect of impaired epithelial chloride and bicarbonate transport. Pregnancy rates were increasing in women with CF. Side effects of mental status changes deserve particular attention in the future.

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Section: Exposure Of Elx/tez/iva To Rare Cftr Geno...mentioning

confidence: 99%

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Tümmler

2023

Front. Pharmacol.

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CFTR Modulator Therapies in Cystic Fibrosis

Spielberg

Clancy

Siracusa

2017

Treatment of Cystic Fibrosis and Other Rare Lung Diseases

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Molecular and Functional Analysis of the Large 5′ Promoter Region of CFTR Gene Revealed Pathogenic Mutations in CF and CFTR-Related Disorders

Giordano

Amato

Elce

et al. 2013

The Journal of Molecular Diagnostics

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Patients with cystic fibrosis (CF) manifest a multisystemic disease due to mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR); despite extensive testing of coding regions, a proportion of CF alleles remains unidentified. We studied 118 patients with CF and CFTR-related disorders, most with one or both unknown mutations after the scanning of CFTR coding regions, and a non-CF control group (n = 75) by sequencing the 6000-bp region at the 5' of the CFTR gene. We identified 23 mutations, of which 9 were novel. We expressed such mutations in vitro using four cell systems to explore their functional effect, relating the data to the clinical expression of each patient. Some mutations reduced expression of the gene reporter firefly luciferase in various cell lines and may act as disease-causing mutations. Other mutations caused an increase in luciferase expression in some cell lines. One mutation had a different effect in different cells. For other mutations, the expression assay excluded a functional role. Gene variants in the large 5' region may cause altered regulation of CFTR gene expression, acting as disease-causing mutations or modifiers of its clinical phenotype. Studies of in vitro expression in different cell systems may help reveal the effect of such mutations.

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CFTR protein analysis of splice site mutation 2789+5 G-A

Cited by 5 publications

References 15 publications

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

CFTR Modulator Therapies in Cystic Fibrosis

Molecular and Functional Analysis of the Large 5′ Promoter Region of CFTR Gene Revealed Pathogenic Mutations in CF and CFTR-Related Disorders

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