Molecular insights into cardiomyopathies associated with desmin (DES) mutations

Ackerman JP, Bartos DC, Kapplinger JD, Tester DJ, Delisle BP, and Ackerman MJ (2016) The promise and peril of precision medicine: phenotyping still matters most. Mayo Clinic proceedings Albers K, Fuchs E (1992) The molecular biology of intermediate filament proteins. Int Rev Cytol 134:243–279 Alonso CR (2005) Nonsense-mediated RNA decay: a molecular system micromanaging individual gene activities and suppressing genomic noise. BioEssays 27:463–466 Ando S, Nakao K, Gohara R, Takasaki Y, Suehiro K, Oishi Y (2004) Morphological analysis of glutaraldehyde-fixed vimentin intermediate filaments and assembly-intermediates by atomic force microscopy. Biochim Biophys Acta 1702:53–65 Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, Sajadieh A, Haunso S, Svendsen JH, Olesen MS (2013) New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet 21:918–928 Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S, Repetto A, Bellini O, Azan G, Scaffino M, Campana C, Piccolo G, Vigano M, Tavazzi L (2006) Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail 8:477–483 Arias M, Pardo J, Blanco-Arias P, Sobrido MJ, Arias S, Dapena D, Carracedo A, Goldfarb LG, Navarro C (2006) Distinct phenotypic features and gender-specific disease manifestations in a Spanish family with desmin L370P mutation. Neuromuscul Disord 16:498–503 Aziz A, Hess JF, Budamagunta MS, FitzGerald PG, Voss JC (2009) Head and rod 1 interactions in vimentin: identification of contact sites, structure, and changes with phosphorylation using site-directed spin labeling and electron paramagnetic resonance. J Biol Chem 284:7330–7338 Aziz A, Hess JF, Budamagunta MS, Voss JC, Fitzgerald PG (2010) Site-directed spin labeling and electron paramagnetic resonance determination of vimentin head domain structure. J Biol Chem 285:15278–15285 Baker LK, Gillis DC, Sharma S, Ambrus A, Herrmann H, Conover GM (2013) Nebulin binding impedes mutant desmin filament assembly. Mol Biol Cell 24:1918–1932 Bar H, Mucke N, Kostareva A, Sjoberg G, Aebi U, Herrmann H (2005a) Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages. Proc Natl Acad Sci U S A 102:15099–15104 Bar H, Fischer D, Goudeau B, Kley RA, Clemen CS, Vicart P, Herrmann H, Vorgerd M, Schroder R (2005b) Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro. Hum Mol Genet 14:1251–1260 Bar H, Mucke N, Ringler P, Muller SA, Kreplak L, Katus HA, Aebi U, Herrmann H (2006) Impact of disease mutations on the desmin filament assembly process. J Mol Biol 360:1031–1042 Bar H, Goudeau B, Walde S, Casteras-Simon M, Mucke N, Shatunov A, Goldberg YP, Clarke C, Holton JL, Eymard B, Katus HA, Fardeau M, Goldfarb L, Vicart P, Herrmann H (2007) Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies. Hum Mutat 28:374–386 Bar H, Schopferer M, Sharma S, Hochstein B, Mucke N, Herrmann H, Willenbacher N (2010) Mutations in desmin's carboxy-terminal “tail” domain severely modify filament and network mechanics. J Mol Biol 397:1188–1198 Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L, Frigo G, Malacrida S, Settimo L, Danieli G, Thiene G, Nava A (2005) Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations. Eur Heart J 26:1666–1675 Becker B, Bellin RM, Sernett SW, Huiatt TW, Robson RM (1995) Synemin contains the rod domain of intermediate filaments. Biochem Biophys Res Commun 213:796–802 Bellin RM, Sernett SW, Becker B, Ip W, Huiatt TW, Robson RM (1999) Molecular characteristics and interactions of the intermediate filament protein synemin. Interactions with alpha-actinin may anchor synemin-containing heterofilaments. J Biol Chem 274:29493–29499 Bellin RM, Huiatt TW, Critchley DR, Robson RM (2001) Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar Z-lines and costameres. J Biol Chem 276:32330–32337 Bergman JE, Veenstra-Knol HE, van Essen AJ, van Ravenswaaij CM, den Dunnen WF, van den Wijngaard A, van Tintelen JP (2007) Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene. Eur J Med Genet 50:355–366 Bermudez-Jimenez, F. J., V. Carriel, A. Brodehl, M. Alaminos, A. Campos, I. Schirmer, H. Milting, B. Alvarez Abril, M. Alvarez, S. Lopez-Fernandez, D. Garcia-Giustiniani, L. Monserrat, L. Tercedor, and J. Jimenez-Jaimez. 2017. The novel desmin mutation p.Glu401Asp impairs filament formation, disrupts cell membrane integrity and causes severe arrhythmogenic left ventricular cardiomyopathy/dysplasia. Circulation Bhosle RC, Michele DE, Campbell KP, Li Z, Robson RM (2006) Interactions of intermediate filament protein synemin with dystrophin and utrophin. Biochem Biophys Res Commun 346:768–777 Bhuiyan ZA, Jongbloed JD, van der Smagt J, Lombardi PM, Wiesfeld AC, Nelen M, Schouten M, Jongbloed R, Cox MG, van Wolferen M, Rodriguez LM, van Gelder IC, Bikker H, Suurmeijer AJ, van den Berg MP, Mannens MM, Hauer RN, Wilde AA, van Tintelen JP (2009) Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study. Circ Cardiovasc Genet 2:418–427 Bilak SR, Sernett SW, Bilak MM, Bellin RM, Stromer MH, Huiatt TW, Robson RM (1998) Properties of the novel intermediate filament protein synemin and its identification in mammalian muscle. Arch Biochem Biophys 355:63–76 Bonakdar N, Luczak J, Lautscham L, Czonstke M, Koch TM, Mainka A, Jungbauer T, Goldmann WH, Schroder R, Fabry B (2012) Biomechanical characterization of a desminopathy in primary human myoblasts. Biochem Biophys Res Commun 419:703–707 Brayson D, Shanahan CM (2017) Current insights into LMNA cardiomyopathies: existing models and missing LINCs. Nucleus 8:17–33 Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120 Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Saric T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H (2012a) Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem 287:16047–16057 Brodehl A, Schmidt T, Gummert J, Milting H (2012b) Molecular insights into filament assembly defects of ARVC-related desmin mutations. Cardiovasc Res 93:S38–S38 Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T, Gargus J, Fatima A, Saric T, Cakar H, Walhorn V, Tonsing K, Skrzipczyk T, Cebulla R, Gerdes D, Schulz U, Gummert J, Svendsen JH, Olesen MS, Anselmetti D, Christensen AH, Kimonis V, Milting H (2013a) The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death. Circ Cardiovasc Genet 6:615–623 Brodehl A, Dieding M, Cakar H, Klauke B, Walhorn V, Gummert J, Anselmetti D, Milting H (2013b) Functional characterization of desmin mutant p.P419S. Eur J Hum Genet 21:589–590 Brodehl A, Dieding M, Biere N, Unger A, Klauke B, Walhorn V, Gummert J, Schulz U, Linke WA, Gerull B, Vorgert M, Anselmetti D, Milting H (2016a) Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect. J Mol Cell Cardiol 91:207–214 Brodehl A, Ferrier RA, Hamilton SJ, Greenway SC, Brundler MA, Yu W, Gibson WT, McKinnon ML, McGillivray B, Alvarez N, Giuffre M, Schwartzentruber J, Consortium FC, Gerull B (2016b) Mutations in FLNC are associated with familial restrictive cardiomyopathy. Hum Mutat 37:269–279 Brodehl A, Belke DD, Garnett L, Martens K, Abdelfatah N, Rodriguez M, Diao C, Chen YX, Gordon PM, Nygren A, Gerull B (2017a) Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling. PLoS One 12:e0174019 Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschroder A, Faber L, Vorgerd M, Gummert J, Anselmetti D, Schulz U, Paluszkiewicz L, Milting H (2017b) The novel alphaB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Hum Mutat 38:947–952 Cabet E, Batonnet-Pichon S, Delort F, Gausseres B, Vicart P, Lilienbaum A (2015) Antioxidant treatment and induction of autophagy cooperate to reduce desmin aggregation in a cellular model of desminopathy. PLoS One 10:e0137009 Cahill TJ, Ashrafian H, Watkins H (2013) Genetic cardiomyopathies causing heart failure. Circ Res 113:660–675 Cao L, Hong D, Zhu M, Li X, Wan H, Hong K (2013) A novel heterozygous deletion-insertion mutation in the desmin gene causes complete atrioventricular block and mild myopathy. Clin Neuropathol 32:9–15 Capetanaki Y, Milner DJ, Weitzer G (1997) Desmin in muscle formation and maintenance: knockouts and consequences. Cell Struct Funct 22:103–116 Capetanaki Y, Papathanasiou S, Diokmetzidou A, Vatsellas G, Tsikitis M (2015) Desmin related disease: a matter of cell survival failure. Curr Opin Cell Biol 32:113–120 Carlsson L, Thornell LE (2001) Desmin-related myopathies in mice and man. Acta Physiol Scand 171:341–348 Cerino M, Gorokhova S, Laforet P, Ben Yaou R, Salort-Campana E, Pouget J, Attarian S, Eymard B, Deleuze JF, Boland A, Behin A, Stojkovic T, Bonne G, Levy N, Bartoli M, Krahn M (2017) Genetic characterization of a French cohort of GNE-mutation negative inclusion body myopathy patients with exome sequencing. Muscle Nerve 56:993–997 Cetin N, Balci-Hayta B, Gundesli H, Korkusuz P, Purali N, Talim B, Tan E, Selcen D, Erdem-Ozdamar S, Dincer P (2013) A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies. J Med Genet 50:437–443 Charrier EE, Asnacios A, Milloud R, De Mets R, Balland M, Delort F, Cardoso O, Vicart P, Batonnet-Pichon S, Henon S (2016) Desmin mutation in the C-terminal domain impairs traction force generation in myoblasts. Biophys J 110:470–480 Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ (2002) Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta-catenin signaling. J Biol Chem 277:10512–10522 Chen F, Chang R, Trivedi M, Capetanaki Y, Cryns VL (2003) Caspase proteolysis of desmin produces a dominant-negative inhibitor of intermediate filaments and promotes apoptosis. J Biol Chem 278:6848–6853 Chen Y, Barajas-Martinez H, Zhu D, Wang X, Chen C, Zhuang R, Shi J, Wu X, Tao Y, Jin W, Wang X, Hu D (2017) Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome. J Transl Med 15:78 Chernyatina AA, Nicolet S, Aebi U, Herrmann H, Strelkov SV (2012) Atomic structure of the vimentin central alpha-helical domain and its implications for intermediate filament assembly. Proc Natl Acad Sci U S A 109:13620–13625 Chernyatina AA, Guzenko D, Strelkov SV (2015) Intermediate filament structure: the bottom-up approach. Curr Opin Cell Biol 32:65–72 Chitaev NA, Averbakh AZ, Troyanovsky RB, Troyanovsky SM (1998) Molecular organization of the desmoglein-plakoglobin complex. J Cell Sci 111(Pt 14):1941–1949 Choi HJ, Park-Snyder S, Pascoe LT, Green KJ, Weis WI (2002) Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure. Nat Struct Biol 9:612–620 Chourbagi O, Bruston F, Carinci M, Xue Z, Vicart P, Paulin D, Agbulut O (2011) Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly. Exp Cell Res 317:886–897 Clemen CS, Stockigt F, Strucksberg KH, Chevessier F, Winter L, Schutz J, Bauer R, Thorweihe JM, Wenzel D, Schlotzer-Schrehardt U, Rasche V, Krsmanovic P, Katus HA, Rottbauer W, Just S, Muller OJ, Friedrich O, Meyer R, Herrmann H, Schrickel JW, Schroder R (2015) The toxic effect of R350P mutant desmin in striated muscle of man and mouse. Acta Neuropathol 129:297–315 Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M (2017) A method for the acute and rapid degradation of endogenous proteins. Cell 171(1692–1706):e1618 Colakoglu G, Brown A (2009) Intermediate filaments exchange subunits along their length and elongate by end-to-end annealing. J Cell Biol 185:769–777 Conover GM, Henderson SN, Gregorio CC (2009) A myopathy-linked desmin mutation perturbs striated muscle actin filament architecture. Mol Biol Cell 20:834–845 Coulombe PA (2017) The molecular revolution in cutaneous biology: keratin genes and their associated disease: diversity, opportunities, and challenges. J Invest Dermatol 137:e67–e71 Crooke ST, Witztum JL, Bennett CF, Baker BF (2018) RNA-targeted therapeutics. Cell Metab 27:714–739 Dagvadorj A, Goudeau B, Hilton-Jones D, Blancato JK, Shatunov A, Simon-Casteras M, Squier W, Nagle JW, Goldfarb LG, Vicart P (2003) Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal alpha-helical segment. Muscle Nerve 27:669–675 Dagvadorj A, Olive M, Urtizberea JA, Halle M, Shatunov A, Bonnemann C, Park KY, Goebel HH, Ferrer I, Vicart P, Dalakas MC, Goldfarb LG (2004) A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin. J Neurol 251:143–149 Dal Ferro M, Stolfo D, Altinier A, Gigli M, Perrieri M, Ramani F, Barbati G, Pivetta A, Brun F, Monserrat L, Giacca M, Mestroni L, Merlo M, Sinagra G (2017) Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy. Heart 103:1704–1710 Dalakas MC, Park KY, Semino-Mora C, Lee HS, Sivakumar K, Goldfarb LG (2000) Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med 342:770–780 Dalakas MC, Dagvadorj A, Goudeau B, Park KY, Takeda K, Simon-Casteras M, Vasconcelos O, Sambuughin N, Shatunov A, Nagle JW, Sivakumar K, Vicart P, Goldfarb LG (2003) Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. Neuromuscul Disord 13:252–258 Dieding M, Debus JD, Kerkhoff R, Gaertner-Rommel A, Walhorn V, Milting H, Anselmetti D (2017) Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics. Sci Rep 7:13791 Diermeier S, Iberl J, Vetter K, Haug M, Pollmann C, Reischl B, Buttgereit A, Schurmann S, Sporrer M, Goldmann WH, Fabry B, Elhamine F, Stehle R, Pfitzer G, Winter L, Clemen CS, Herrmann H, Schroder R, Friedrich O (2017a) Early signs of architectural and biomechanical failure in isolated myofibers and immortalized myoblasts from desmin-mutant knock-in mice. Sci Rep 7:1391 Diermeier S, Buttgereit A, Schurmann S, Winter L, Xu H, Murphy RM, Clemen CS, Schroder R, Friedrich O (2017b) Preaged remodeling of myofibrillar cytoarchitecture in skeletal muscle expressing R349P mutant desmin. Neurobiol Aging 58:77–87 Dubin RA, Wawrousek EF, Piatigorsky J (1989) Expression of the murine alpha B-crystallin gene is not restricted to the lens. Mol Cell Biol 9:1083–1091 Dunand M, Lobrinus JA, Jeannet PY, Behin A, Claeys KG, Selcen D, Kuntzer T (2009) Confirmation that abnormal desmin accumulation and migration are due to a desmin gene mutation in a familial cardiomyopathy and distal myopathy. Neuromuscul Disord 19:802 Durmus H, Ayhan O, Cirak S, Deymeer F, Parman Y, Franke A, Eiber N, Chevessier F, Schlotzer-Schrehardt U, Clemen CS, Hashemolhosseini S, Schroder R, Hemmrich-Stanisak G, Tolun A, Serdaroglu-Oflazer P (2016) Neuromuscular endplate pathology in recessive desminopathies: lessons from man and mice. Neurology 87:799–805 Elliott JL, Der Perng M, Prescott AR, Jansen KA, Koenderink GH, Quinlan RA (2013) The specificity of the interaction between alphaB-crystallin and desmin filaments and its impact on filament aggregation and cell viability. Philos Trans R Soc Lond Ser B Biol Sci 368:20120375 Even C, Abramovici G, Delort F, Rigato AF, Bailleux V, de Sousa Moreira A, Vicart P, Rico F, Batonnet-Pichon S, Briki F (2017) Mutation in the core structure of desmin intermediate filaments affects myoblast elasticity. Biophys J 113:627–636 Fichna JP, Karolczak J, Potulska-Chromik A, Miszta P, Berdynski M, Sikorska A, Filipek S, Redowicz MJ, Kaminska A, Zekanowski C (2014) Two desmin gene mutations associated with myofibrillar myopathies in Polish families. PLoS One 9:e115470 Fidzianska A, Kotowicz J, Sadowska M, Goudeau B, Walczak E, Vicart P, Hausmanowa-Petrusewicz I (2005) A novel desmin R355P mutation causes cardiac and skeletal myopathy. Neuromuscul Disord 15:525–531 Fischer D, Clemen CS, Olive M, Ferrer I, Goudeau B, Roth U, Badorf P, Wattjes MP, Lutterbey G, Kral T, van der Ven PF, Furst DO, Vicart P, Goldfarb LG, Moza M, Carpen O, Reichelt J, Schroder R (2006) Different early pathogenesis in myotilinopathy compared to primary desminopathy. Neuromuscul Disord 16:361–367 Fokstuen S, Makrythanasis P, Hammar E, Guipponi M, Ranza E, Varvagiannis K, Santoni FA, Albarca-Aguilera M, Poleggi ME, Couchepin F, Brockmann C, Mauron A, Hurst SA, Moret C, Gehrig C, Vannier A, Bevillard J, Araud T, Gimelli S, Stathaki E, Paoloni-Giacobino A, Bottani A, Sloan-Bena F, Sizonenko LD, Mostafavi M, Hamamy H, Nouspikel T, Blouin JL, Antonarakis SE (2016) Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders. Hum Genom 10:24 Garcia-Pelagio KP, Chen L, Joca HC, Ward C, Jonathan Lederer W, Bloch RJ (2018) Absence of synemin in mice causes structural and functional abnormalities in heart. J Mol Cell Cardiol 114:354–363 Gard JJ, Yamada K, Green KG, Eloff BC, Rosenbaum DS, Wang X, Robbins J, Schuessler RB, Yamada KA, Saffitz JE (2005) Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. Cardiovasc Res 67:539–547 Garrido C, Paul C, Seigneuric R, Kampinga HH (2012) The small heat shock proteins family: the long forgotten chaperones. Int J Biochem Cell Biol 44:1588–1592 Gehmlich K, Lambiase PD, Asimaki A, Ciaccio EJ, Ehler E, Syrris P, Saffitz JE, McKenna WJ (2011) A novel desmocollin-2 mutation reveals insights into the molecular link between desmosomes and gap junctions. Heart Rhythm 8:711–718 Gehmlich K, Syrris P, Reimann M, Asimaki A, Ehler E, Evans A, Quarta G, Pantazis A, Saffitz JE, McKenna WJ (2012) Molecular changes in the heart of a severe case of arrhythmogenic right ventricular cardiomyopathy caused by a desmoglein-2 null allele. Cardiovasc Pathol 21:275–282 Geisler N, Kaufmann E, Weber K (1985) Antiparallel orientation of the two double-stranded coiled-coils in the tetrameric protofilament unit of intermediate filaments. J Mol Biol 182:173–177 Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG (1990) A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 62:999–1006 Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L (2004) Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36:1162–1164 Goebel HH (1997) Desmin-related myopathies. Curr Opin Neurol 10:426–429 Goebel HH, Muller HD (2006) Protein aggregate myopathies. Semin Pediatr Neurol 13:96–103 Golbus JR, Puckelwartz MJ, Dellefave-Castillo L, Fahrenbach JP, Nelakuditi V, Pesce LL, Pytel P, McNally EM (2014) Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy. Circ Cardiovasc Genet 7:751–759 Goldfarb LG, Dalakas MC (2009) Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. J Clin Invest 119:1806–1813 Goldfarb LG, Park KY, Cervenakova L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC (1998) Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 19:402–403 Goudeau B, Dagvadorj A, Rodrigues-Lima F, Nedellec P, Casteras-Simon M, Perret E, Langlois S, Goldfarb L, Vicart P (2001) Structural and functional analysis of a new desmin variant causing desmin-related myopathy. Hum Mutat 18:388–396 Goudeau B, Rodrigues-Lima F, Fischer D, Casteras-Simon M, Sambuughin N, de Visser M, Laforet P, Ferrer X, Chapon F, Sjoberg G, Kostareva A, Sejersen T, Dalakas MC, Goldfarb LG, Vicart P (2006) Variable pathogenic potentials of mutations located in the desmin alpha-helical domain. Hum Mutat 27:906–913 Granger BL, Lazarides E (1980) Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle. Cell 22:727–738 Gudkova A, Kostareva A, Sjoberg G, Smolina N, Turalchuk M, Kuznetsova I, Rybakova M, Edstrom L, Shlyakhto E, Sejersen T (2013) Diagnostic challenge in desmin cardiomyopathy with transformation of clinical phenotypes. Pediatr Cardiol 34:467–470 Guzman C, Jeney S, Kreplak L, Kasas S, Kulik AJ, Aebi U, Forro L (2006) Exploring the mechanical properties of single vimentin intermediate filaments by atomic force microscopy. J Mol Biol 360:623–630 Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, Feng Z, Muller S, Kayvanpour E, Vogel B, Sedaghat-Hamedani F, Lim WK, Zhao X, Fradkin D, Kohler D, Fischer S, Franke J, Marquart S, Barb I, Li DT, Amr A, Ehlermann P, Mereles D, Weis T, Hassel S, Kremer A, King V, Wirsz E, Isnard R, Komajda M, Serio A, Grasso M, Syrris P, Wicks E, Plagnol V, Lopes L, Gadgaard T, Eiskjaer H, Jorgensen M, Garcia-Giustiniani D, Ortiz-Genga M, Crespo-Leiro MG, Deprez RH, Christiaans I, van Rijsingen IA, Wilde AA, Waldenstrom A, Bolognesi M, Bellazzi R, Morner S, Bermejo JL, Monserrat L, Villard E, Mogensen J, Pinto YM, Charron P, Elliott P, Arbustini E, Katus HA, Meder B (2015) Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J 36:1123–1135a Harada H, Hayashi T, Nishi H, Kusaba K, Koga Y, Koga Y, Nonaka I, Kimura A (2018) Phenotypic expression of a novel desmin gene mutation: hypertrophic cardiomyopathy followed by systemic myopathy. J Hum Genet 63:249–254 Harder A, Dieding M, Walhorn V, Degenhard S, Brodehl A, Wege C, Milting H, Anselmetti D (2013) Apertureless scanning near-field optical microscopy of sparsely labeled tobacco mosaic viruses and the intermediate filament desmin. Beilstein J Nanotechnol 4:510–516 Harrison OJ, Brasch J, Lasso G, Katsamba PS, Ahlsen G, Honig B, Shapiro L (2016) Structural basis of adhesive binding by desmocollins and desmogleins. Proc Natl Acad Sci U S A 113:7160–7165 Haskell GT, Jensen BC, Samsa LA, Marchuk D, Huang W, Skrzynia C, Tilley C, Seifert BA, Rivera-Munoz EA, Koller B, Wilhelmsen KC, Liu JD, Alhosaini H, Weck KE, Evans JP, Berg JS (2017) Whole exome sequencing identifies truncating variants in nuclear envelope genes in patients with cardiovascular disease. Circ Cardiovasc Genet 10 Hatzfeld M, Weber K (1992) A synthetic peptide representing the consensus sequence motif at the carboxy-terminal end of the rod domain inhibits intermediate filament assembly and disassembles preformed filaments. J Cell Biol 116:157–166 Heckmann MB, Bauer R, Jungmann A, Winter L, Rapti K, Strucksberg KH, Clemen CS, Li Z, Schroder R, Katus HA, Muller OJ (2016) AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice. Gene Ther 23:673–679 Hedberg C, Melberg A, Kuhl A, Jenne D, Oldfors A (2012) Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation. Eur J Human Genet 20:984–985 Hedberg C, Melberg A, Kuhl A, Jenne D, Oldfors A (2013) Reply to Brodehl et al. Eur J Hum Genet 21:590 Hedde PN, Gayda S, Brodehl A, Gummert J, Milting H, Nienhaus GU (2012) Colocalization analysis of mutant and wildtype desmin using dual color super-resolution microscopy. Biophys J 102:722a–722a Henderson M, De Waele L, Hudson J, Eagle M, Sewry C, Marsh J, Charlton R, He L, Blakely EL, Horrocks I, Stewart W, Taylor RW, Longman C, Bushby K, Barresi R (2013) Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities. Acta Neuropathol 125:917–919 Herrmann H, Aebi U (2004) Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem 73:749–789 Herrmann H, Strelkov SV (2011) History and phylogeny of intermediate filaments: now in insects. BMC Biol 9:16 Herrmann H, Haner M, Brettel M, Muller SA, Goldie KN, Fedtke B, Lustig A, Franke WW, Aebi U (1996) Structure and assembly properties of the intermediate filament protein vimentin: the role of its head, rod and tail domains. J Mol Biol 264:933–953 Herrmann H, Strelkov SV, Feja B, Rogers KR, Brettel M, Lustig A, Haner M, Parry DA, Steinert PM, Burkhard P, Aebi U (2000) The intermediate filament protein consensus motif of helix 2B: its atomic structure and contribution to assembly. J Mol Biol 298:817–832 Herrmann H, Bar H, Kreplak L, Strelkov SV, Aebi U (2007) Intermediate filaments: from cell architecture to nanomechanics. Nat Rev Mol Cell Biol 8:562–573 Herrmann H, Strelkov SV, Burkhard P, Aebi U (2009) Intermediate filaments: primary determinants of cell architecture and plasticity. J Clin Invest 119:1772–1783 Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B (2006) Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 79:1081–1088 Hirako Y, Yamakawa H, Tsujimura Y, Nishizawa Y, Okumura M, Usukura J, Matsumoto H, Jackson KW, Owaribe K, Ohara O (2003) Characterization of mammalian synemin, an intermediate filament protein present in all four classes of muscle cells and some neuroglial cells: co-localization and interaction with type III intermediate filament proteins and keratins. Cell Tissue Res 313:195–207 Hnia K, Ramspacher C, Vermot J, Laporte J (2015) Desmin in muscle and associated diseases: beyond the structural function. Cell Tissue Res 360:591–608 Hofmann I, Mertens C, Brettel M, Nimmrich V, Schnolzer M, Herrmann H (2000) Interaction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis. J Cell Sci 113(Pt 13):2471–2483 Hong DJ, Zhang W, Jiang TY, Feng L, Wang ZX, Yuan Y (2010) Clinical characteristics and desmin mutations in patients with desminopathy associated cardiomyopathy from 5 Chinese families. Zhonghua xin xue guan bing za zhi 38:420–424 Hong D, Wang Z, Zhang W, Xi J, Lu J, Luan X, Yuan Y (2011) A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene. Neuropathol Appl Neurobiol 37:257–270 Izant JG, Lazarides E (1977) Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis. Proc Natl Acad Sci U S A 74:1450–1454 Jaka O, Casas-Fraile L, Lopez de Munain A, Saenz A (2015) Costamere proteins and their involvement in myopathic processes. Expert Rev Mol Med 17:e12 Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821 Joanne P, Chourbagi O, Hourde C, Ferry A, Butler-Browne G, Vicart P, Dumonceaux J, Agbulut O (2013) Viral-mediated expression of desmin mutants to create mouse models of myofibrillar myopathy. Skelet Muscle 3:4 Jurcu TR, Bastian AE, Militaru S, Popa A, Manole E, Popescu BA, Tallila J, Popescu BO, Ginghina CD (2017) Discovery of a new mutation in the desmin gene in a young patient with cardiomyopathy and muscular weakness. Rom J Morphol Embryol 58:225–230 Kami K, Chidgey M, Dafforn T, Overduin M (2009) The desmoglein-specific cytoplasmic region is intrinsically disordered in solution and interacts with multiple desmosomal protein partners. J Mol Biol 386:531–543 Kaminska A, Strelkov SV, Goudeau B, Olive M, Dagvadorj A, Fidzianska A, Simon-Casteras M, Shatunov A, Dalakas MC, Ferrer I, Kwiecinski H, Vicart P, Goldfarb LG (2004) Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy. Hum Genet 114:306–313 Kaufmann E, Weber K, Geisler N (1985) Intermediate filament forming ability of desmin derivatives lacking either the amino-terminal 67 or the carboxy-terminal 27 residues. J Mol Biol 185:733–742 Khudiakov A, Kostina D, Zlotina A, Nikulina T, Sergushichev A, Gudkova A, Tomilin A, Malashicheva A, Kostareva A (2017) Generation of iPSC line from desmin-related cardiomyopathy patient carrying splice site mutation of DES gene. Stem Cell Res 24:77–80 Kiss B, Kellermayer MS (2014) Stretching desmin filaments with receding meniscus reveals large axial tensile strength. J Struct Biol 186:472–480 Kiss B, Karsai A, Kellermayer MS (2006) Nanomechanical properties of desmin intermediate filaments. J Struct Biol 155:327–339 Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Knyphausen EZ, Vorgerd M, Gummert J, Milting H (2010) De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet 19:4595–4607 Kooijman M, van Amerongen H, Traub P, van Grondelle R, Bloemendal M (1995) The assembly state of the intermediate filament proteins desmin and glial fibrillary acidic protein at low ionic strength. FEBS Lett 358:185–188 Kostareva A, Gudkova A, Sjoberg G, Kiselev I, Moiseeva O, Karelkina E, Goldfarb L, Schlyakhto E, Sejersen T (2006) Desmin mutations in a St. Petersburg cohort of cardiomyopathies. Acta Myologica Myopathies Cardiomyopathies 25:109–115 Kostareva A, Sjoberg G, Bruton J, Zhang SJ, Balogh J, Gudkova A, Hedberg B, Edstrom L, Westerblad H, Sejersen T (2008) Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria. J Muscle Res Cell Motil 29:25–36 Kostareva A, Sjoberg G, Gudkova A, Smolina N, Semernin E, Shlyakhto E, Sejersen T (2011) Desmin A213V substitution represents a rare polymorphism but not a mutation and is more prevalent in patients with heart dilation of various origins. Acta Myologica 30:42–45 Kreplak L, Bar H (2009) Severe myopathy mutations modify the nanomechanics of desmin intermediate filaments. J Mol Biol 385:1043–1051 Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, Jang W, Katz K, Ovetsky M, Riley G, Sethi A, Tully R, Villamarin-Salomon R, Rubinstein W, Maglott DR (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44:D862–D868 Lapouge K, Fontao L, Champliaud MF, Jaunin F, Frias MA, Favre B, Paulin D, Green KJ, Borradori L (2006) New insights into the molecular basis of desmoplakin- and desmin-related cardiomyopathies. J Cell Sci 119:4974–4985 Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, C. Exome Aggregation (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–291 Levin J, Bulst S, Thirion C, Schmidt F, Botzel K, Krause S, Pertl C, Kretzschmar H, Walter MC, Giese A, Lochmuller H (2010) Divergent molecular effects of desmin mutations on protein assembly in myofibrillar myopathy. J Neuropathol Exp Neurol 69:415–424 Li ZL, Lilienbaum A, Butler-Browne G, Paulin D (1989) Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development. Gene 78:243–254 Li Z, Colucci-Guyon E, Pincon-Raymond M, Mericskay M, Pournin S, Paulin D, Babinet C (1996) Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 175:362–366 Li D, Tapscoft T, Gonzalez O, Burch PE, Quinones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R (1999) Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation 100:461–464 Li M, Andersson-Lendahl M, Sejersen T, Arner A (2013) Knockdown of desmin in zebrafish larvae affects interfilament spacing and mechanical properties of skeletal muscle. J Gen Physiol 141:335–345 Lin YC, Broedersz CP, Rowat AC, Wedig T, Herrmann H, Mackintosh FC, Weitz DA (2010) Divalent cations crosslink vimentin intermediate filament tail domains to regulate network mechanics. J Mol Biol 399:637–644 Liu J, Chen Q, Huang W, Horak KM, Zheng H, Mestril R, Wang X (2006a) Impairment of the ubiquitin-proteasome system in desminopathy mouse hearts. FASEB J 20:362–364 Liu J, Tang M, Mestril R, Wang X (2006b) Aberrant protein aggregation is essential for a mutant desmin to impair the proteolytic function of the ubiquitin-proteasome system in cardiomyocytes. J Mol Cell Cardiol 40:451–454 Lorenzon A, Beffagna G, Bauce B, De Bortoli M, Li Mura IE, Calore M, Dazzo E, Basso C, Nava A, Thiene G, Rampazzo A (2013) Desmin mutations and arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 111:400–405 Lund LM, Kerr JP, Lupinetti J, Zhang Y, Russell MA, Bloch RJ, Bond M (2012) Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes. FASEB J 26:137–148 Maddison P, Damian MS, Sewry C, McGorrian C, Winer JB, Odgerel Z, Shatunov A, Lee HS, Goldfarb LG (2012) Clinical and myopathological characteristics of desminopathy caused by a mutation in desmin tail domain. Eur Neurol 68:279–286 Maerkens A, Kley RA, Olive M, Theis V, van der Ven PF, Reimann J, Milting H, Schreiner A, Uszkoreit J, Eisenacher M, Barkovits K, Guttsches AK, Tonillo J, Kuhlmann K, Meyer HE, Schroder R, Tegenthoff M, Furst DO, Muller T, Goldfarb LG, Vorgerd M, Marcus K (2013) Differential proteomic analysis of abnormal intramyoplasmic aggregates in desminopathy. J Proteome 90:14–27 Maerkens A, Olive M, Schreiner A, Feldkirchner S, Schessl J, Uszkoreit J, Barkovits K, Guttsches AK, Theis V, Eisenacher M, Tegenthoff M, Goldfarb LG, Schroder R, Schoser B, van der Ven PF, Furst DO, Vorgerd M, Marcus K, Kley RA (2016) New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses. Acta Neuropathol Commun 4:8 Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, Imahashi K, Murphy E, Robbins J (2005) Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation 112:3451–3461 Maloyan A, Sayegh J, Osinska H, Chua BH, Robbins J (2010) Manipulation of death pathways in desmin-related cardiomyopathy. Circ Res 106:1524–1532 Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB, A. American Heart, H. F. Council on Clinical Cardiology, C. Transplantation, C. Quality of, R. Outcomes, G. Functional, G. Translational Biology Interdisciplinary Working, E. Council on, and Prevention (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807–1816 Matsushita N, Hirose M, Sanbe A, Kondo Y, Irie Y, Taira E (2014) Nicorandil improves electrical remodelling, leading to the prevention of electrically induced ventricular tachyarrhythmia in a mouse model of desmin-related cardiomyopathy. Clin Exp Pharmacol Physiol 41:89–97 McCormick EM, Kenyon L, Falk MJ (2015) Desmin common mutation is associated with multi-systemic disease manifestations and depletion of mitochondria and mitochondrial DNA. Front Genet 6:199 McKenna WJ, Maron BJ, Thiene G (2017) Classification, epidemiology, and global burden of cardiomyopathies. Circ Res 121:722–730 McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, McKenna WJ (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119–2124 McLaughlin HM, Kelly MA, Hawley PP, Darras BT, Funke B, Picker J (2013) Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy. BMC Med Genet 14:68 McLendon PM, Robbins J (2011) Desmin-related cardiomyopathy: an unfolding story. Am J Physiol Heart Circ Physiol 301:H1220–H1228 Mencarelli C, Ciolfi S, Caroti D, Lupetti P, Dallai R (2011) Isomin: a novel cytoplasmic intermediate filament protein from an arthropod species. BMC Biol 9:17 Miszalski-Jamka K, Jefferies JL, Mazur W, Glowacki J, Hu J, Lazar M, Gibbs RA, Liczko J, Klys J, Venner E, Muzny DM, Rycaj J, Bialkowski J, Kluczewska E, Kalarus Z, Jhangiani S, Al-Khalidi H, Kukulski T, Lupski JR, Craigen WJ, Bainbridge MN (2017) Novel genetic triggers and genotype-phenotype correlations in patients with left ventricular noncompaction. Circ Cardiovasc Genet 10 Monies D, Abouelhoda M, AlSayed M, Alhassnan Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al Saud BK, Kurdi W, Makhseed N, Alqasim T, El Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout R, Dabbagh O, Shagrani M, Broering D, Tulbah M, Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh H, AlGhonaium A, Alkharfy TM, Al Mutairi F, Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, Alenizi AS, Hussein MH, Hassan S, Khalil M, Tabarki B, Alshahwan S, Oshi A, Sabr Y, Alsaadoun S, Salih MA, Mohamed S, Sultana H, Tamim A, El-Haj M, Alshahrani S, Bubshait DK, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, Shah Z, Moghrabi N, Meyer BF, Alkuraya FS (2017) The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet 136:921–939 Mook OR, Haagmans MA, Soucy JF, van de Meerakker JB, Baas F, Jakobs ME, Hofman N, Christiaans I, Lekanne Deprez RH, Mannens MM (2013) Targeted sequence capture and GS-FLX titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics. J Med Genet 50:614–626 Munoz-Marmol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernandez-Figueras MT, Navas-Palacios JJ, Ariza A, Fuchs E (1998) A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Natl Acad Sci U S A 95:11312–11317 Muntoni F, Bonne G, Goldfarb LG, Mercuri E, Piercy RJ, Burke M, Yaou RB, Richard P, Recan D, Shatunov A, Sewry CA, Brown SC (2006) Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain J Neurol 129:1260–1268 Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG, N. I. H. I. S. C. C. S. Program (2013) Interpreting secondary cardiac disease variants in an exome cohort. Circ Cardiovasc Genet 6:337–346 Nouhravesh N, Ahlberg G, Ghouse J, Andreasen C, Svendsen JH, Haunso S, Bundgaard H, Weeke PE, Olesen MS (2016) Analyses of more than 60,000 exomes questions the role of numerous genes previously associated with dilated cardiomyopathy. Mol Genet Genomic Med 4:617–623 Ojrzynska N, Bilinska ZT, Franaszczyk M, Ploski R, Grzybowski J (2017) Restrictive cardiomyopathy due to novel desmin gene mutation. Kardiol Pol 75:723 Olive M, Goldfarb L, Dagvadorj A, Sambuughin N, Paulin D, Li Z, Goudeau B, Vicart P, Ferrer I (2003) Expression of the intermediate filament protein synemin in myofibrillar myopathies and other muscle diseases. Acta Neuropathol 106:1–7 Olive M, Armstrong J, Miralles F, Pou A, Fardeau M, Gonzalez L, Martinez F, Fischer D, Martinez Matos JA, Shatunov A, Goldfarb L, Ferrer I (2007) Phenotypic patterns of desminopathy associated with three novel mutations in the desmin gene. Neuromuscul Disord 17:443–450 Olive M, Odgerel Z, Martinez A, Poza JJ, Bragado FG, Zabalza RJ, Jerico I, Gonzalez-Mera L, Shatunov A, Lee HS, Armstrong J, Maravi E, Arroyo MR, Pascual-Calvet J, Navarro C, Paradas C, Huerta M, Marquez F, Rivas EG, Pou A, Ferrer I, Goldfarb LG (2011) Clinical and myopathological evaluation of early- and late-onset subtypes of myofibrillar myopathy. Neuromuscul Disord 21:533–542 Osborn M, Goebel HH (1983) The cytoplasmic bodies in a congenital myopathy can be stained with antibodies to desmin, the muscle-specific intermediate filament protein. Acta Neuropathol 62:149–152 Palmio J, Penttila S, Huovinen S, Haapasalo H, Udd B (2013) An unusual phenotype of late-onset desminopathy. Neuromuscul Disord 23:922–923 Park KY, Dalakas MC, Semino-Mora C, Lee HS, Litvak S, Takeda K, Ferrans VJ, Goldfarb LG (2000a) Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation. Clin Genet 57:423–429 Park KY, Dalakas MC, Goebel HH, Ferrans VJ, Semino-Mora C, Litvak S, Takeda K, Goldfarb LG (2000b) Desmin splice variants causing cardiac and skeletal myopathy. J Med Genet 37:851–857 Patel DM, Green KJ (2014) Desmosomes in the heart: a review of clinical and mechanistic analyses. Cell Commun Adhes 21:109–128 Pica EC, Kathirvel P, Pramono ZA, Lai PS, Yee WC (2008) Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family. Neuromuscul Disord 18:178–182 Pinol-Ripoll G, Shatunov A, Cabello A, Larrode P, de la Puerta I, Pelegrin J, Ramos FJ, Olive M, Goldfarb LG (2009) Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin. Neuromuscul Disord 19:418–422 Plodinec M, Loparic M, Suetterlin R, Herrmann H, Aebi U, Schoenenberger CA (2011) The nanomechanical properties of rat fibroblasts are modulated by interfering with the vimentin intermediate filament system. J Struct Biol 174:476–484 Potschka M, Nave R, Weber K, Geisler N (1990) The two coiled coils in the isolated rod domain of the intermediate filament protein desmin are staggered. A hydrodynamic analysis of tetramers and dimers. Eur J Biochem 190:503–508 Price MG, Lazarides E (1983) Expression of intermediate filament-associated proteins paranemin and synemin in chicken development. J Cell Biol 97:1860–1874 Pruszczyk P, Kostera-Pruszczyk A, Shatunov A, Goudeau B, Draminska A, Takeda K, Sambuughin N, Vicart P, Strelkov SV, Goldfarb LG, Kaminska A (2007) Restrictive cardiomyopathy with atrioventricular conduction block resulting from a desmin mutation. Int J Cardiol 117:244–253 Psarras S, Mavroidis M, Sanoudou D, Davos CH, Xanthou G, Varela AE, Panoutsakopoulou V, Capetanaki Y (2012) Regulation of adverse remodelling by osteopontin in a genetic heart failure model. Eur Heart J 33:1954–1963 Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH (2014) The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med 16:601–608 Punetha J, Kesari A, Uapinyoying P, Giri M, Clarke NF, Waddell LB, North KN, Ghaoui R, O'Grady GL, Oates EC, Sandaradura SA, Bonnemann CG, Donkervoort S, Plotz PH, Smith EC, Tesi-Rocha C, Bertorini TE, Tarnopolsky MA, Reitter B, Hausmanowa-Petrusewicz I, Hoffman EP (2016) Targeted re-sequencing emulsion PCR panel for myopathies: results in 94 cases. J Neuromuscul Dis 3:209–225 Raats JM, Schaart G, Henderik JB, van der Kemp A, Dunia I, Benedetti EL, Pieper FR, Ramaekers FC, Bloemendal H (1996) Muscle-specific expression of a dominant negative desmin mutant in transgenic mice. Eur J Cell Biol 71:221–236 Rainer PP, Dong P, Sorge M, Fert-Bober J, Holewinski RJ, Wang Y, Foss C, An SS, Baracca A, Solaini G, Glabe C, Pomper MG, Van Eyk JE, Tomaselli GF, Paolocci N, Agnetti G (2018) Desmin phosphorylation triggers preamyloid oligomers formation and myocyte dysfunction in acquired heart failure. Circ Res Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, Zhang XQ, Stevenson TJ, Peshock RM, Leopold JA, Barry WH, Loscalzo J, Odelberg SJ, Benjamin IJ (2007) Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:427–439 Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA (2002) Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 71:1200–1206 Ramspacher C, Steed E, Boselli F, Ferreira R, Faggianelli N, Roth S, Spiegelhalter C, Messaddeq N, Trinh L, Liebling M, Chacko N, Tessadori F, Bakkers J, Laporte J, Hnia K, Vermot J (2015) Developmental alterations in heart biomechanics and skeletal muscle function in desmin mutants suggest an early pathological root for desminopathies. Cell Rep 11:1564–1576 Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ALQA (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424 Ripoll-Vera T, Zorio E, Gamez JM, Molina P, Govea N, Cremer D (2015) Phenotypic patterns of cardiomyopathy caused by mutations in the desmin gene. A clinical and genetic study in two inherited heart disease units. Rev Esp Cardiol 68:1027–1029 Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A, Robbins J (2004) Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A 101:10132–10136 Sanbe A, Daicho T, Mizutani R, Endo T, Miyauchi N, Yamauchi J, Tanonaka K, Glabe C, Tanoue A (2009) Protective effect of geranylgeranylacetone via enhancement of HSPB8 induction in desmin-related cardiomyopathy. PLoS One 4:e5351 Sanbe A, Marunouchi T, Yamauchi J, Tanonaka K, Nishigori H, Tanoue A (2011) Cardioprotective effect of nicorandil, a mitochondrial ATP-sensitive potassium channel opener, prolongs survival in HSPB5 R120G transgenic mice. PLoS One 6:e18922 Schanzer A, Rupp S, Graf S, Zengeler D, Jux C, Akinturk H, Gulatz L, Mazhari N, Acker T, Van Coster R, Garvalov BK, Hahn A (2018) Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3. Mol Genet Metab 123:388–399 Schirmer I, Dieding M, Klauke B, Brodehl A, Gaertner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H (2018) A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Mol Genet Genomic Med 6(2):288–293 Schrickel JW, Stockigt F, Krzyzak W, Paulin D, Li Z, Lubkemeier I, Fleischmann B, Sasse P, Linhart M, Lewalter T, Nickenig G, Lickfett L, Schroder R, Clemen CS (2010) Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice. J Interv Card Electrophysiol 28:71–80 Schroder JM, Sommer C, Schmidt B (1990) Desmin and actin associated with cytoplasmic bodies in skeletal muscle fibers: immunocytochemical and fine structural studies, with a note on unusual 18- to 20-nm filaments. Acta Neuropathol 80:406–414 Schroder R, Goudeau B, Simon MC, Fischer D, Eggermann T, Clemen CS, Li ZL, Reimann J, Xue ZG, Rudnik-Schoneborn S, Zerres K, van der Ven PFM, Furst DO, Kunz WS, Vicart P (2003) On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria. Hum Mol Genet 12:657–669 Schroder R, Goudeau B, Simon MC, Fischer D, Eggermann T, Clemen CS, Li ZL, Reimann J, Xue ZG, Rudnik-Schoneborn S, Zerres K, van der Ven PFM, Furst DO, Kunz WS, Vicart P (2007) On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria (vol 12, pg 657, 2003). Hum Mol Genet 16:2989–2990 Schwarz N, Leube RE (2016) Intermediate filaments as organizers of cellular space: how they affect mitochondrial structure and function. Cells 5 Selcen D, Ohno K, Engel AG (2004) Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain J Neurol 127:439–451 Shanks GW, Tester DJ, Nishtala S, Evans JM, Ackerman MJ (2017) Genomic triangulation and coverage analysis in whole-exome sequencing-based molecular autopsies. Circ Cardiovasc Genet 10 Sharma S, Mucke N, Katus HA, Herrmann H, Bar H (2009) Disease mutations in the “head” domain of the extra-sarcomeric protein desmin distinctly alter its assembly and network-forming properties. J Mol Med 87:1207–1219 Sjoberg G, Saavedra-Matiz CA, Rosen DR, Wijsman EM, Borg K, Horowitz SH, Sejersen T (1999) A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation. Hum Mol Genet 8:2191–2198 Smolina N, Bruton J, Sjoberg G, Kostareva A, Sejersen T (2014) Aggregate-prone desmin mutations impair mitochondrial calcium uptake in primary myotubes. Cell Calcium 56:269–275 van Spaendonck-Zwarts KY, van Hessem L, Jongbloed JD, de Walle HE, Capetanaki Y, van der Kooi AJ, van Langen IM, van den Berg MP, van Tintelen JP (2011) Desmin-related myopathy. Clin Genet 80:354–366 van Spaendonck-Zwarts KY, van der Kooi AJ, van den Berg MP, Ippel EF, Boven LG, Yee WC, van den Wijngaard A, Brusse E, Hoogendijk JE, Doevendans PA, de Visser M, Jongbloed JD, van Tintelen JP (2012) Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D. Neth Hear J 20:219–228 van Spaendonck-Zwarts KY, van Rijsingen IA, van den Berg MP, Lekanne Deprez RH, Post JG, van Mil AM, Asselbergs FW, Christiaans I, van Langen IM, Wilde AA, de Boer RA, Jongbloed JD, Pinto YM, van Tintelen JP (2013) Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: overview of 10 years’ experience. Eur J Heart Fail 15:628–636 Sprinkart AM, Block W, Traber F, Meyer R, Paulin D, Clemen CS, Schroder R, Gieseke J, Schild H, Thomas D (2012) Characterization of the failing murine heart in a desmin knock-out model using a clinical 3 T MRI scanner. Int J Card Imaging 28:1699–1705 Stoeckel ME, Osborn M, Porte A, Sacrez A, Batzenschlager A, Weber K (1981) An unusual familial cardiomyopathy characterized by aberrant accumulations of desmin-type intermediate filaments. Virchows Archiv A Pathological Anat Histol 393:53–60 Strach K, Sommer T, Grohe C, Meyer C, Fischer D, Walter MC, Vorgerd M, Reilich P, Bar H, Reimann J, Reuner U, Germing A, Goebel HH, Lochmuller H, Wintersperger B, Schroder R (2008) Clinical, genetic, and cardiac magnetic resonance imaging findings in primary desminopathies. Neuromuscul Disord 18:475–482 Sugawara M, Kato K, Komatsu M, Wada C, Kawamura K, Shindo PS, Yoshioka PN, Tanaka K, Watanabe S, Toyoshima I (2000) A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates. Neurology 55:986–990 Sun N, Critchley DR, Paulin D, Li Z, Robson RM (2008) Human alpha-synemin interacts directly with vinculin and metavinculin. Biochem J 409:657–667 Szeverenyi I, Cassidy AJ, Chung CW, Lee BT, Common JE, Ogg SC, Chen H, Sim SY, Goh WL, Ng KW, Simpson JA, Chee LL, Eng GH, Li B, Lunny DP, Chuon D, Venkatesh A, Khoo KH, McLean WH, Lim YP, Lane EB (2008) The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases. Hum Mutat 29:351–360 Taylor MR, Slavov D, Ku L, Di Lenarda A, Sinagra G, Carniel E, Haubold K, Boucek MM, Ferguson D, Graw SL, Zhu X, Cavanaugh J, Sucharov CC, Long CS, Bristow MR, Lavori P, Mestroni L, R. Familial Cardiomyopathy, B. D. Bank (2007) Prevalence of desmin mutations in dilated cardiomyopathy. Circulation 115:1244–1251 Thornell L, Carlsson L, Li Z, Mericskay M, Paulin D (1997) Null mutation in the desmin gene gives rise to a cardiomyopathy. J Mol Cell Cardiol 29:2107–2124 Tian C, Fuller C, Miles L, Jefferies J, Ryan T, Sawnani H, Bolger A, Wong B (2016) A novel homozygous desmin nonsense mutation causes pediatric onset autosomal recessive desminopathy with severe cardiomyopathy. Neuromuscul Disord 26:S114–S115 van Tintelen JP, Van Gelder IC, Asimaki A, Suurmeijer AJ, Wiesfeld AC, Jongbloed JD, van den Wijngaard A, Kuks JB, van Spaendonck-Zwarts KY, Notermans N, Boven L, van den Heuvel F, Veenstra-Knol HE, Saffitz JE, Hofstra RM, van den Berg MP (2009) Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene. Heart Rhythm 6:1574–1583 Tse HF, Ho JC, Choi SW, Lee YK, Butler AW, Ng KM, Siu CW, Simpson MA, Lai WH, Chan YC, Au KW, Zhang J, Lay KW, Esteban MA, Nicholls JM, Colman A, Sham PC (2013) Patient-specific induced-pluripotent stem cells-derived cardiomyocytes recapitulate the pathogenic phenotypes of dilated cardiomyopathy due to a novel DES mutation identified by whole exome sequencing. Hum Mol Genet 22:1395–1403 Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Ponten F (2015) Proteomics. Tissue-based map of the human proteome. Science 347:1260419 Vattemi G, Neri M, Piffer S, Vicart P, Gualandi F, Marini M, Guglielmi V, Filosto M, Tonin P, Ferlini A, Tomelleri G (2011) Clinical, morphological and genetic studies in a cohort of 21 patients with myofibrillar myopathy. Acta Myologica 30:121–126 Vernengo L, Chourbagi O, Panuncio A, Lilienbaum A, Batonnet-Pichon S, Bruston F, Rodrigues-Lima F, Mesa R, Pizzarossa C, Demay L, Richard P, Vicart P, Rodriguez MM (2010) Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon deletion in a new location within the desmin 1A rod domain. Neuromuscul Disord 20:178–187 Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A, Chateau D, Chapon F, Tome F, Dupret JM, Paulin D, Fardeau M (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20:92–95 Wahbi K, Behin A, Charron P, Dunand M, Richard P, Meune C, Vicart P, Laforet P, Stojkovic T, Becane HM, Kuntzer T, Duboc D (2012) High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10-year longitudinal study. Neuromuscul Disord 22:211–218 Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, C. Exome Aggregation, MacArthur DG, Farrall M, Cook SA, Watkins H (2017) Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med 19:192–203 Walter MC, Reilich P, Huebner A, Fischer D, Schroder R, Vorgerd M, Kress W, Born C, Schoser BG, Krause KH, Klutzny U, Bulst S, Frey JR, Lochmuller H (2007) Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P. Brain J Neurol 130:1485–1496 Wang X, Osinska H, Klevitsky R, Gerdes AM, Nieman M, Lorenz J, Hewett T, Robbins J (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res 89:84–91 Weihl CC, Iyadurai S, Baloh RH, Pittman SK, Schmidt RE, Lopate G, Pestronk A, Harms MB (2015) Autophagic vacuolar pathology in desminopathies. Neuromuscul Disord 25:199–206 Wilson KD, Shen P, Fung E, Karakikes I, Zhang A, InanlooRahatloo K, Odegaard J, Sallam K, Davis RW, Lui GK, Ashley EA, Scharfe C, Wu JC (2015) A rapid, high-quality, cost-effective, comprehensive and expandable targeted next-generation sequencing assay for inherited heart diseases. Circ Res 117:603–611 Winheim S, Hieb AR, Silbermann M, Surmann EM, Wedig T, Herrmann H, Langowski J, Mucke N (2011) Deconstructing the late phase of vimentin assembly by total internal reflection fluorescence microscopy (TIRFM). PLoS One 6:e19202 Winter L, Wittig I, Peeva V, Eggers B, Heidler J, Chevessier F, Kley RA, Barkovits K, Strecker V, Berwanger C, Herrmann H, Marcus K, Kornblum C, Kunz WS, Schroder R, Clemen CS (2016) Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue. Acta Neuropathol 132:453–473 Yla-Herttuala S, Baker AH (2017) Cardiovascular gene therapy: past, present, and future. Mol Ther 25:1095–1106 Yu M, Zheng Y, Jin S, Gang Q, Wang Q, Yu P, Lv H, Zhang W, Yuan Y, Wang Z (2017a) Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing. PLoS One 12:e0175343 Yu R, Liu L, Chen C, Shen JM (2017b) Exome sequencing identifies a novel DES mutation (R227C) in a Chinese dilated cardiomyopathy family. Cardiology 137:78–82 Zhao F, Chaugai S, Chen P, Wang Y, Wang DW (2014) Effect of nicorandil in patients with heart failure: a systematic review and meta-analysis. Cardiovasc Ther 32:283–296 Zhao Y, Feng Y, Zhang YM, Ding XX, Song YZ, Zhang AM, Liu L, Zhang H, Ding JH, Xia XS (2015) Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy. Int J Mol Med 36:1479–1486 Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF, McSweeney KM, Ben-Zeev B, Nissenkorn A, Anikster Y, Oz-Levi D, Dhindsa RS, Hitomi Y, Schoch K, Spillmann RC, Heimer G, Marek-Yagel D, Tzadok M, Han Y, Worley G, Goldstein J, Jiang YH, Lancet D, Pras E, Shashi V, McHale D, Need AC, Goldstein DB (2015) Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. Genet Med 17:774–781