Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin c-terminal alpha-helical segment

Muscle & Nerve
Ayush DagvadorjPatrick Vicart

Abstract

Mutations in desmin gene have been identified in patients with cardiac and skeletal myopathy characterized by intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates. We characterized two new desminopathy families with unusual features of adult-onset, slowly progressive, diffuse skeletal myopathy and respiratory insufficiency. Progressive reduction of respiratory muscle strength became clinically detectable between the 3rd and the 8th years of illness and led to recurrent chest infections and death in one of the patients. Novel mutations, A357P and L370P, predicted to introduce proline residue into a highly conserved alpha-helical region of desmin, were identified. Proline is known to disrupt the alpha-helix. In addition, the A357P mutation distorts a unique stutter sequence that is considered to be critically important for proper filament assembly. Functional assessment in two cell-lines, one of which does and the other of which does not constitutively produce type III intermediate filaments, demonstrated the inability of mutant desmin carrying either the A357P or the L370P mutation to polymerize and form an intracellular filamentous network. The results of this study indicate that resp...Continue Reading

References

Mar 20, 1991·Journal of Molecular Biology·M W MacArthur, J M Thornton
Apr 1, 1986·Experimental Cell Research·K K Hedberg, L B Chen
Nov 1, 1995·Muscle & Nerve·H H Goebel
Jan 1, 1994·Annual Review of Biochemistry·E Fuchs, K Weber
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M Muñoz-MármolE Fuchs
Oct 16, 1999·Cellular and Molecular Life Sciences : CMLS·H Herrmann, U Aebi
Mar 16, 2000·The New England Journal of Medicine·M C DalakasL G Goldfarb
Jul 25, 2000·Clinical Genetics·K Y ParkL G Goldfarb
Nov 10, 2000·Journal of Medical Genetics·K Y ParkL G Goldfarb
Dec 21, 2000·American Journal of Physiology. Cell Physiology·A M BoriekJ G Tidball
Feb 13, 2001·Trends in Cell Biology·P BurkhardS V Strelkov
Mar 21, 2001·Neuromuscular Disorders : NMD·L PolitanoG Nigro
May 23, 2001·Circulation·X WangJ Robbins

❮ Previous
Next ❯

Citations

Nov 13, 2012·Acta Neuropathologica·Christoph S ClemenRolf Schröder
Mar 31, 2004·Journal of the Neurological Sciences·Montse OlivéIsidro Ferrer
Sep 4, 2008·Expert Reviews in Molecular Medicine·Isidre Ferrer, Montse Olivé
Oct 11, 2011·Biologie aujourd'hui·Pierre JoanneOnnik Agbulut
Jan 4, 2007·Pathology International·Takashi YuriAiro Tsubura
Jul 10, 2009·The Journal of Clinical Investigation·Lev G Goldfarb, Marinos C Dalakas
Apr 24, 2014·Cell Communication & Adhesion·Dipal M Patel, Kathleen J Green
Nov 3, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·J Peter van TintelenMaarten P van den Berg
Oct 21, 2004·The Journal of Pathology·Denise PaulinZhigang Xue
May 28, 2008·Neuromuscular Disorders : NMD·Katharina StrachRolf Schröder
Jan 26, 2005·Annals of Neurology·Duygu Selcen, Andrew G Engel
Dec 27, 2005·European Journal of Heart Failure·Eloisa ArbustiniLuigi Tavazzi
Aug 20, 2010·Clinical Genetics·K Y van Spaendonck-ZwartsJ P van Tintelen
Sep 8, 2015·Revue neurologique·A BéhinB Eymard
May 11, 2006·Neuromuscular Disorders : NMD·Dirk FischerRolf Schröder
Jul 13, 2005·Neuromuscular Disorders : NMD·Anna FidziańskaIrena Hausmanowa-Petrusewicz
Dec 30, 2014·PloS One·Jakub Piotr FichnaCezary Zekanowski
Dec 6, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Mark J RanekMonte S Willis
Jun 22, 2018·Biophysics Reviews·Andreas BrodehlHendrik Milting
Feb 28, 2007·Circulation·Matthew R G TaylorUNKNOWN BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank
Sep 8, 2020·Journal of Cachexia, Sarcopenia and Muscle·Henning T LangerKeith Baar
Apr 7, 2021·Scientific Reports·Gülsüm Kayman KürekçiPervin R Dincer
Apr 28, 2004·Neurology·Duygu Selcen, Andrew G Engel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.