A 3'-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome

Human Molecular Genetics
Marina DuslAngela Abicht

Abstract

Mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) cause the neuromuscular disorder limb-girdle congenital myasthenic syndrome (LG-CMS). One recurrent GFPT1 mutation detected in LG-CMS patients is a c.*22C>A transversion in the 3'-untranslated region (UTR). Because this variant does not alter the GFPT1 open reading frame, its pathogenic relevance has not yet been established. We found that GFPT1 protein levels were reduced in myoblast cells of the patients carrying this variant. In silico algorithms predicted that the mutation creates a microRNA target site for miR-206*. Investigation of the expression of this so far unrecognized microRNA confirmed that miR-206* (like its counterpart miR-206) is abundant in skeletal muscle. MiR-206* efficiently reduced the expression of reporter constructs containing the mutated 3'-UTR while no such effect was observed with reporter constructs containing the wild-type 3'-UTR or when a specific anti-miR-206* inhibitor was added. Moreover, anti-miR-206* inhibitor treatment substantially rescued GFPT1 expression levels in patient-derived myoblasts. Our data demonstrate that the c.*22C>A mutation in the GFPT1 gene leads to illegitimate binding of microRNA resulting...Continue Reading

References

Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 26, 2003·Nucleic Acids Research·Ivo L Hofacker
Oct 22, 2003·Cell·Dianne S SchwarzPhillip D Zamore
Dec 30, 2003·Genes, Chromosomes & Cancer·Markus MetzlerArndt Borkhardt
Mar 12, 2004·Genes & Development·John G Doench, Phillip A Sharp
Nov 9, 2004·Nature·Ahmet M DenliGregory J Hannon
Jan 12, 2005·Briefings in Functional Genomics & Proteomics·Hervé ChabanonJohn Hesketh
Feb 22, 2005·PLoS Biology·Julius BrenneckeStephen M Cohen
Oct 15, 2005·Science·Jesse F AbelsonMatthew W State
May 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Prakash K RaoHarvey F Lodish
Aug 23, 2006·The Journal of Cell Biology·Hak Kyun KimAnindya Dutta
Apr 27, 2007·American Journal of Physiology. Cell Physiology·John J McCarthyFrancisco H Andrade
Jun 15, 2007·Expert Reviews in Molecular Medicine·Lucy R Osborne, Carolyn B Mervis
Jul 7, 2007·Molecular Cell·Andrew GrimsonDavid P Bartel
Oct 16, 2007·Developmental Biology·Jason R O'RourkeBrian D Harfe
Oct 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Iris EisenbergLouis M Kunkel
Jan 29, 2008·Experimental Biology and Medicine·Thomas E CallisDa-Zhi Wang
Apr 1, 2008·Nature Structural & Molecular Biology·Katsutomo OkamuraEric C Lai
Apr 3, 2008·Biochimica Et Biophysica Acta·John J McCarthy
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Amy N PackerBeverly L Davidson
Mar 13, 2009·Current Opinion in Cell Biology·Andrew H WilliamsEric N Olson
Jun 19, 2009·Nature·Sung Wook ChiRobert B Darnell
Jul 14, 2010·Molecular Cell·Chanseok ShinDavid P Bartel
Oct 15, 2011·Current Neurology and Neuroscience Reports·Andrew G Engel
Mar 26, 2014·PloS One·Gregorio ValdezJoshua R Sanes

❮ Previous
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Citations

Jan 21, 2016·European Journal of Human Genetics : EJHG·Amandine I GarciaSylvie Mazoyer
Jan 2, 2016·Biochimica Et Biophysica Acta·Anke P WillemsDirk J Lefeber
Dec 2, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ming-Liang JiChen Wang
Oct 17, 2018·Journal of Medical Genetics·Stefano PaolacciRaoul C Hennekam
Sep 3, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marta UnoltDonna McDonald-McGinn
Oct 19, 2017·Nucleic Acids Research·Jing GongQiangfeng Cliff Zhang
Jul 30, 2016·Current Opinion in Neurology·David Beeson
Jun 26, 2020·Molecular Biology and Evolution·Andrea Hatlen, Antonio Marco
Nov 8, 2015·Médecine sciences : M/S·Valérie Allamand
Feb 22, 2017·The Journal of Clinical Investigation·Kashan AhmedMarkus Stoffel
Feb 28, 2019·Orphanet Journal of Rare Diseases·Josef Finsterer
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Katarzyna I JankowskaChintamani D Atreya
Aug 6, 2020·Neurology. Genetics·Szabolcs SzelingerUNKNOWN UCLA Clinical Genomics Center

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