Gene expression profiling of fibroblasts in a family with LMNA-related cardiomyopathy reveals molecular pathways implicated in disease pathogenesis

BMC Medical Genetics
Halida P WidyastutiMichael V Zaragoza

Abstract

Intermediate filament proteins that construct the nuclear lamina of a cell include the Lamin A/C proteins encoded by the LMNA gene, and are implicated in fundamental processes such as nuclear structure, gene expression, and signal transduction. LMNA mutations predominantly affect mesoderm-derived cell lineages in diseases collectively termed as laminopathies that include dilated cardiomyopathy with conduction defects, different forms of muscular dystrophies, and premature aging syndromes as Hutchinson-Gilford Progeria Syndrome. At present, our understanding of the molecular mechanisms regulating tissue-specific manifestations of laminopathies are still limited. To gain deeper insight into the molecular mechanism of a novel LMNA splice-site mutation (c.357-2A > G) in an affected family with cardiac disease, we conducted deep RNA sequencing and pathway analysis for nine fibroblast samples obtained from three patients with cardiomyopathy, three unaffected family members, and three unrelated, unaffected individuals. We validated our findings by quantitative PCR and protein studies. We identified eight significantly differentially expressed genes between the mutant and non-mutant fibroblasts, that included downregulated insulin grow...Continue Reading

References

May 16, 2000·The Journal of Biological Chemistry·L J SchedlichR C Baxter
Jan 4, 2001·Pacing and Clinical Electrophysiology : PACE·H M BécaneD Duboc
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Mar 19, 2002·Journal of the American College of Cardiology·Eloisa ArbustiniLuigi Tavazzi
Mar 12, 2003·Journal of the American College of Cardiology·Matthew R G TaylorUNKNOWN Familial Dilated Cardiomyopathy Registry Research Group
Apr 19, 2003·Science·Annachiara De Sandre-GiovannoliNicolas Lévy
Aug 9, 2003·Science·Shiv I S Grewal, Danesh Moazed
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Brett R JohnsonBrian K Kennedy
Jul 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Laurent VergnesKaren Reue
Jul 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mario F FragaManel Esteller
Sep 24, 2005·Stem Cells·Dan ConstantinescuAntonei B Csoka
Feb 17, 2006·Genes & Development·Richard L FrockBrian K Kennedy
Apr 21, 2007·The Journal of Clinical Investigation·Antoine MuchirHoward J Worman
Feb 28, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Ying JiangToshimasa Uemura
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Feb 7, 2009·Nature Reviews. Molecular Cell Biology·Diana E Jaalouk, Jan Lammerding
Feb 13, 2009·Journal of Cellular and Molecular Medicine·Miron ProkocimerYosef Gruenbaum
Jun 16, 2009·Biochimica Et Biophysica Acta·Lindsay J EmersonJuliet A Ellis
Jul 25, 2009·The American Journal of Pathology·Hidekata YasuokaCarol A Feghali-Bostwick
Oct 24, 2009·FEBS Letters·Tobias MaierLuis Serrano
Feb 27, 2010·Current Opinion in Cardiology·Lisa Dellefave, Elizabeth M McNally
Sep 2, 2010·Proceedings of the National Academy of Sciences of the United States of America·Guillermo MariñoCarlos López-Otín
Sep 10, 2010·Cold Spring Harbor Perspectives in Biology·Thomas DechatRobert D Goldman
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jun 7, 2011·Genome Biology·Travis A Dittmer, Tom Misteli
Feb 18, 2012·The New England Journal of Medicine·Daniel S HermanChristine E Seidman
Mar 14, 2012·Nature Reviews. Genetics·Christine Vogel, Edward M Marcotte
Apr 14, 2012·Biochemistry Research International·Diana LindnerDirk Westermann
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Sep 20, 2012·Nucleus·Nadia KorfaliEric C Schirmer

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Methods Mentioned

BETA
RNA-seq
biopsies
Biopsy
Protein Assay
PCR

Software Mentioned

TopHat2
FastQC
Tophat
cummeRbund
ImageJ
IPA
cuffdiff2
cufflinks
Integrative Genomics Viewer ( IGV )
BaseSpace Sequence Hub

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