c.3623G > A mutation encodes a CFTR protein with impaired channel function

Respiratory Research
Xiaoying ZhangWeiqiang Zhang

Abstract

The aims of this study were to characterize clinical features of a pediatric African-American cystic fibrosis (CF) patient heterozygous for F508del and a novel c.3623G > A mutation, and to identify the molecular defect(s) associated with c.3623G > A mutation. The medical record of this patient was analyzed retrospectively. Western blotting and iodide efflux assay were used to study mutant CFTR protein expression level, maturation status, channel function, and the effects of CFTR modulation on these characteristics. The encoding protein of c.3623G > A mutation, G1208D-CFTR, has a moderate processing defect and exhibits impaired channel function, which were partially rescued by using VX-809 or exposed to low temperature (28 °C). The patient has mild CF disease manifestations. Our biochemical findings correlate with the clinical phenotype and suggest that c.3623G > A is a CF-causing mutation. The study helps expand our knowledge of rare CFTR mutations in a minority population and may have important clinical implications for personalized therapeutic intervention.

References

Sep 17, 2004·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Elaine A SugarmanBernice A Allitto
Dec 15, 2007·BMJ : British Medical Journal·Jane C DaviesAndrew Bush
May 1, 2009·Lancet·Brian P O'Sullivan, Steven D Freedman
Dec 7, 2010·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Francesca Bresso, Mauro D'Amato
Apr 9, 2011·Clinical Chemistry·Elizabeth M RohlfsElaine A Sugarman
Oct 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Fredrick Van GoorPaul A Negulescu
Feb 9, 2012·American Journal of Respiratory and Critical Care Medicine·Bonnie W RamseyMichael Welsh
Jun 23, 2012·American Journal of Respiratory and Critical Care Medicine·John P Clancy, Manu Jain
Oct 3, 2012·American Journal of Respiratory and Critical Care Medicine·Sunitha YarlagaddaJohn C Kappes

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Citations

Jan 20, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Misak HarutyunyanAnjaparavanda P Naren
Mar 4, 2020·Personalized Medicine·Fouzia RadouaniNicola Mulder

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Methods Mentioned

BETA
protein assay
PCR

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