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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 2012 (10)

Title and authors Publication Year
The susceptibility of T5-TG12 of the CFTR gene in chronic bronchitis occurrence in a Chinese population in Jiangsu province, China
P Wang, S Naruse, H Yin, Z Yu, T Zhuang, W Ding, Y Wu, M Wei
Journal of Biomedical Research 2012
The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens
WH Ni, L Jiang, QJ Fei, JY Jin, X Yang, XF Huang
Asian Journal of Andrology 2012
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens
H Li, Q Wen, H Li, L Zhao, X Zhang, J Wang, L Cheng, J Yang, S Chen, X Ma, B Wang
Journal of Cystic Fibrosis 2012
Regulatory variations in the era of next-generation sequencing: Implications for clinical molecular diagnostics
O Jarinova, M Ekker
Human Mutation 2012
Association of S549N and IVS8-5T Splice Variants with Bronchial Asthma and Its Severity in Indian Children
N Maurya, S Awasthi, P Dixit, S Agarwal
Genetic Testing and Molecular Biomarkers 2012
Kendig & Chernick’s Disorders of the Respiratory Tract in Children
SH Abman
Kendig & Chernick’s Disorders of the Respiratory Tract in Children 2012
Association of CFTR gene mutation with bronchial asthma
N Maurya, S Awasthi, P Dixit
The Indian journal of medical research 2012
Association of cystic fibrosis transmembrane conductance regulator gene variants with acute lung injury in African American children with pneumonia*:
JM Baughn, MW Quasney, P Simpson, D Merchant, SH Li, H Levy, MK Dahmer
Critical Care Medicine 2012
Assessing the Disease-Liability of Mutations in CFTR
C Ferec, GR Cutting
Cold Spring Harbor Perspectives in Medicine 2012
CFTR polymorphisms of healthy individuals in two Chinese cities--Changchun and Nanjing
Chun Xiang Jin, Kotoyo Fujiki, Ying Song, Zhang Ping, Miyuki Nakakuki, Mu Xin Wei, Su Min Zhang, Hiroshi Ishiguro, Satoru Naruse
Nagoya Journal of Medical Science 2012

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