ArticleHuman genetics2005
A neutral variant involved in a complex CFTR allele contributes to a severe cystic fibrosis phenotype.
Article in Human genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Analysis of AlphaMissense data in different protein groups and structural context.Scientific data · 2024Article
- Advances in the Study of Common and RareJournal of personalized medicine · 2024Review
- Benchmarking AlphaMissense Pathogenicity Predictions Against Cystic Fibrosis Variants.bioRxiv : the preprint server for biology · 2024Article
- Benchmarking AlphaMissense pathogenicity predictions against cystic fibrosis variants.PloS one · 2024Article
- The Effect of Complex Alleles of theInternational journal of molecular sciences · 2023Review
- Pharmacological analysis of CFTR variants of cystic fibrosis using stem cell-derived organoids.Drug discovery today · 2019Review
- Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.Experimental & molecular medicine · 2015Article
- N1303K (c.3909C>G) mutation and splicing: implication of its c.[744-33GATT(6); 869+11C>T] complex allele in CFTR exon 7 aberrant splicing.BioMed research international · 2015Article
- A pseudo-dominant form of Gitelman's syndrome.NDT plus · 2011Article
- p.Ser1235Arg should no longer be considered as a cystic fibrosis mutation: results from a large collaborative study.European journal of human genetics : EJHG · 2011Article
- Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.Cancer · 2010Article
- Expression and localization of cystic fibrosis transmembrane conductance regulator in the rat endocrine pancreas.Endocrine · 2007Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to further elucidate the contribution of complex alleles to the wide phenotypic variability of cystic fibrosis (CF), we investigated the structure-function relationships of a severe CF-associated complex allele [p.S912L;p.G1244V]. To evaluate the contribution of each mutation to the phenotype, cystic fibrosis transmembrane conductance regulator (CFTR) mutants were expressed in HeLa cells and analysed for protein processing and Cl- channel activity. Both p.G1244V and [p.S912L;p.G1244V] mutants had normal protein processing but markedly decreased Cl- channel activity compared with wild-type. Notably, the double mutant displayed a dramatic decrease in Cl- channel activity compared with p.G1244V (P<0.001). p.S912L had normal protein processing and no detectable impact on CFTR function. In other respects, the p.S912L variation was identified in compound heterozygosity with p.R709X in a healthy fertile man. Together, these data strongly support the view that p.S912L in isolation should be considered as a neutral variant but one that might significantly impair CFTR function when inherited in cis with another CFTR mutation. Our data also further document the contribution of complex alleles to the wide phenotypic variability of CF. The results of functional studies of such complex alleles in other genetic diseases are discussed.
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