The CFTR frameshift mutation 3905insT and its effect at transcript and protein level

Sanz, Javier; von Känel, Thomas; Schneider, Mircea; Steiner, Bernhard; Schaller, André; Gallati, Sabina (2010). The CFTR frameshift mutation 3905insT and its effect at transcript and protein level. European journal of human genetics, 18(2), pp. 212-7. Houndmills, UK: Nature Publishing Group 10.1038/ejhg.2009.140

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Cystic fibrosis (CF) is one of the most common genetic diseases in the Caucasian population and is characterized by chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevation of sodium and chloride concentrations in the sweat and infertility in men. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as chloride channel at the apical membrane of different epithelia. Owing to the high genotypic and phenotypic disease heterogeneity, effects and consequences of the majority of the CFTR mutations have not yet been studied. Recently, the frameshift mutation 3905insT was identified as the second most frequent mutation in the Swiss population and found to be associated with a severe phenotype. The frameshift mutation produces a premature termination codon (PTC) in exon 20, and transcripts bearing this PTC are potential targets for degradation through nonsense-mediated mRNA decay (NMD) and/or for exon skipping through nonsense-associated alternative splicing (NAS). Using RT-PCR analysis in lymphocytes and different tissue types from patients carrying the mutation, we showed that the PTC introduced by the mutation does neither elicit a degradation of the mRNA through NMD nor an alternative splicing through NAS. Moreover, immunocytochemical analysis in nasal epithelial cells revealed a significantly reduced amount of CFTR at the apical membrane providing a possible molecular explanation for the more severe phenotype observed in F508del/3905insT compound heterozygotes compared with F508del homozygotes. However, further experiments are needed to elucidate the fate of the 3905insT CFTR in the cell after its biosynthesis.

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Journal Article (Original Article)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology > Centre of Competence for Psychosomatic Medicine

UniBE Contributor:

von Känel, Thomas; Schneider, Mircea; Schaller, André and Gallati, Sabina




Nature Publishing Group




Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

04 May 2014 23:04

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URI: (FactScience: 196594)

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