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Citations to this article

Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.
H Cuppens, … , B Nilius, J J Cassiman
H Cuppens, … , B Nilius, J J Cassiman
Published January 15, 1998
Citation Information: J Clin Invest. 1998;101(2):487-496. https://doi.org/10.1172/JCI639.
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Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.

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Abstract

In congenital bilateral absence of the vas deferens patients, the T5 allele at the polymorphic Tn locus in the CFTR (cystic fibrosis transmembrane conductance regulator) gene is a frequent disease mutation with incomplete penetrance. This T5 allele will result in a high proportion of CFTR transcripts that lack exon 9, whose translation products will not contribute to apical chloride channel activity. Besides the polymorphic Tn locus, more than 120 polymorphisms have been described in the CFTR gene. We hypothesized that the combination of particular alleles at several polymorphic loci might result in less functional or even insufficient CFTR protein. Analysis of three polymorphic loci with frequent alleles in the general population showed that, in addition to the known effect of the Tn locus, the quantity and quality of CFTR transcripts and/or proteins was affected by two other polymorphic loci: (TG)m and M470V. On a T7 background, the (TG)11 allele gave a 2.8-fold increase in the proportion of CFTR transcripts that lacked exon 9, and (TG)12 gave a sixfold increase, compared with the (TG)10 allele. T5 CFTR genes derived from patients were found to carry a high number of TG repeats, while T5 CFTR genes derived from healthy CF fathers harbored a low number of TG repeats. Moreover, it was found that M470 CFTR proteins matured more slowly, and that they had a 1.7-fold increased intrinsic chloride channel activity compared with V470 CFTR proteins, suggesting that the M470V locus might also play a role in the partial penetrance of T5 as a disease mutation. Such polyvariant mutant genes could explain why apparently normal CFTR genes cause disease. Moreover, they might be responsible for variation in the phenotypic expression of CFTR mutations, and be of relevance in other genetic diseases.

Authors

H Cuppens, W Lin, M Jaspers, B Costes, H Teng, A Vankeerberghen, M Jorissen, G Droogmans, I Reynaert, M Goossens, B Nilius, J J Cassiman

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 Total
Citations: 1 5 6 3 6 13 5 7 10 12 6 8 11 10 29 14 14 14 21 17 27 22 7 13 10 10 11 3 315
Citation information
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Citations to this article in year 2005 (27)

Title and authors Publication Year
Misprocessing of theCFTR protein leads to mild cystic fibrosis phenotype
J Clain, J Lehmann-Che, I Dugu�p�roux, N Arous, E Girodon, M Legendre, M Goossens, A Edelman, M Braekeleer, J Teulon, P Fanen
Human Mutation 2005
Cystic fibrosis lung disease: genetic influences, microbial interactions, and radiological assessment
SM Moskowitz, RL Gibson, EL Effmann
Pediatric Radiology 2005
Reduced CFTR Function and the Pathobiology of Idiopathic Pancreatitis
JA Cohn
Journal of Clinical Gastroenterology 2005
Variations of theCFTR gene in the Hanoi-Vietnamese
MH Nam, M Hijikata, LA Tuan, LT Lien, J Shojima, T Horie, K Nakata, I Matsushita, J Ohashi, K Tokunaga, N Keicho
American Journal of Medical Genetics Part A 2005
Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls
FU Weiss, P Simon, N Bogdanova, J Mayerle, B Dworniczak, J Horst, MM Lerch
Gut 2005
Direct molecular haplotyping by melting curve analysis of hybridization probes: beta 2-adrenergic receptor haplotypes as an example
G Pont-Kingdon, E Lyon
Nucleic Acids Research 2005
Cystic fibrosis in Korean children:a case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis
KM Ahn, HY Park, JH Lee, MG Lee, JH Kim, IJ Kang, SI Lee
Journal of Korean Medical Science 2005
Cystic fibrosis modifier genes
J Davies, E Alton, U Griesenbach
Journal of the Royal Society of Medicine 2005
MODIFIER GENETICS: Cystic Fibrosis
GR Cutting
Annual Review of Genomics and Human Genetics 2005
Gene SNPs and mutations in clinical genetic testing: haplotype-based testing and analysis
JE Lee, JH Choi, JH Lee, MG Lee
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2005
The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis
MD Bishop, SD Freedman, J Zielenski, N Ahmed, A Dupuis, S Martin, L Ellis, J Shea, I Hopper, M Corey, P Kortan, G Haber, C Ross, J Tzountzouris, L Steele, PN Ray, LC Tsui, PR Durie
Human Genetics 2005
Lack of Association of Common Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations with Primary Sclerosing Cholangitis
JF Gallegos-Orozco, CE Yurk, N Wang, J Rakela, MR Charlton, GR Cutting, V Balan
The American Journal of Gastroenterology 2005
Modifier genes in cystic fibrosis
JC Davies, U Griesenbach, E Alton
Pediatric Pulmonology 2005
Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations
F Pompei, BM Ciminelli, C Bombieri, C Ciccacci, M Koudova, S Giorgi, F Belpinati, A Begnini, M Cerny, MD Georges, M Claustres, C Ferec, M Macek, G Modiano, PF Pignatti
European Journal of Human Genetics 2005
Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs
L Stuppia, I Antonucci, F Binni, A Brandi, N Grifone, A Colosimo, MD Santo, V Gatta, G Gelli, V Guida, S Majore, G Calabrese, C Palka, A Ravani, R Rinaldi, GM Tiboni, E Ballone, A Venturoli, A Ferlini, I Torrente, P Grammatico, E Calzolari, B Dallapiccola
European Journal of Human Genetics 2005
Alternative pre-mRNA splicing in the human system: unexpected role of repetitive sequences as regulatory elements
J Hui, A Bindereif
Biological Chemistry 2005
Certain Background Factors Exhibit an Association With an Increased Risk for Pancreatic Calcification Among Japanese Male Alcoholics
Y Nakamura, T Ohmori, S Higuchi, K Maruyama
Pancreas 2005
Molecular pathology of the CFTR locus in male infertility
M Claustres
Reproductive BioMedicine Online 2005
Identification of Putative New Splicing Targets for ETR-3 Using Sequences Identified by Systematic Evolution of Ligands by Exponential Enrichment
NA Faustino, TA Cooper
Molecular and cellular biology 2005
Human, Drosophila, and C.elegans TDP43: Nucleic Acid Binding Properties and Splicing Regulatory Function
YM Ayala, S Pantano, A D'Ambrogio, E Buratti, A Brindisi, C Marchetti, M Romano, FE Baralle
Journal of Molecular Biology 2005
Lung Biology in Health and Disease: Cellular and Molecular Mechanisms
E Sapey, R Stockley
Lung Biology in Health and Disease: Experimental Models and Therapeutic Potential 2005
The Impact of Cystic Fibrosis and PSTI/SPINK1 Gene Mutations on Susceptibility to Chronic Pancreatitis
JA Cohn, RM Mitchell, PS Jowell
Clinics in Laboratory Medicine 2005
Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study
M Dahl, A Tybjærg-Hansen, P Lange, BG Nordestgaard
Respiratory Research 2005
Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens
CC Wu, ÖM Alper, JF Lu, SP Wang, L Guo, HS Chiang, LJ Wong
Human Reproduction 2005
Cystic Fibrosis Prenatal Screening in Genetic Counseling Practice: Recommendations of the National Society of Genetic Counselors
E Langfelder-Schwind, E Kloza, E Sugarman, B Pettersen, T Brown, K Jensen, S Marcus, J Redman
Journal of Genetic Counseling 2005
Direct Molecular Haplotyping of the IVS-8 Poly(TG) and PolyT Repeat Tracts in the Cystic Fibrosis Gene by Melting Curve Analysis of Hybridization Probes
A Millson, G Pont-Kingdon, S Page, E Lyon
Clinical chemistry 2005
Cystic fibrosis: terminology and diagnostic algorithms.
De Boeck K, Wilschanski M, Castellani C, Taylor C, Cuppens H, Dodge J, Sinaasappel M
Thorax 2005

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