Phenotypic Patterns of Desminopathy Associated with Three Novel Mutations in the Desmin Gene

Overview

Journal Neuromuscul Disord

Specialty Neurology

Date 2007 Apr 10

PMID 17418574

Citations 24

Authors

Montse Olive

Judith Armstrong

Francesc Miralles

Adolf Pou

Michel Fardeau

Laura Gonzalez

Francesca Martinez

Dirk Fischer

Juan Antonio Martinez Matos

Alexey Shatunov

Lev Goldfarb

Isidre Ferrer

Affiliations

Soon will be listed here.

Abstract

Desminopathy represents a subgroup of myofibrillar myopathies caused by mutations in the desmin gene. Three novel disease-associated mutations in the desmin gene were identified in unrelated Spanish families affected by cardioskeletal myopathy. A selective pattern of muscle involvement, which differed from that observed in myofibrillar myopathy resulting from mutations in the myotilin gene, was observed in each of the three families with novel mutations and each of three desminopathy patients with known desmin mutations. Prominent joint retractions at the ankles and characteristic nasal speech were observed early in the course of illness. These findings suggest that muscle imaging in combination with routine clinical and pathological examination may be helpful in distinguishing desminopathy from other forms of myofibrillar myopathy and ordering appropriate molecular investigations.

Citing Articles

The Myocardial Accumulation of Aggregated Desmin Protein in a Case of Desminopathy with a de novo DES p.R406W Mutation.

Takegami N, Mitsutake A, Mano T, Shintani-Domoto Y, Unuma A, Yamaguchi-Takegami N Intern Med. 2023; 62(19):2883-2887.

PMID: 36792195 PMC: 10602824. DOI: 10.2169/internalmedicine.0992-22.

Desmin variants: Trigger for cardiac arrhythmias?.

Su W, van Wijk S, Brundel B Front Cell Dev Biol. 2022; 10:986718.

PMID: 36158202 PMC: 9500482. DOI: 10.3389/fcell.2022.986718.

Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.

Yang A, Lin N, Yeh T, Snider N, Perng M Mol Biol Cell. 2022; 33(8):ar69.

PMID: 35511821 PMC: 9635275. DOI: 10.1091/mbc.E22-01-0013.

Genetic Insights into Primary Restrictive Cardiomyopathy.

Brodehl A, Gerull B J Clin Med. 2022; 11(8).

PMID: 35456187 PMC: 9027761. DOI: 10.3390/jcm11082094.

Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction.

Kubanek M, Schimerova T, Piherova L, Brodehl A, Krebsova A, Ratnavadivel S J Clin Med. 2020; 9(4).

PMID: 32235386 PMC: 7231262. DOI: 10.3390/jcm9040937.

References

Dagvadorj A, Olive M, Urtizberea J, Halle M, Shatunov A, Bonnemann C . A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin. J Neurol. 2004; 251(2):143-9. DOI: 10.1007/s00415-004-0289-3. View

Kaminska A, Strelkov S, Goudeau B, Olive M, Dagvadorj A, Fidzianska A . Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy. Hum Genet. 2003; 114(3):306-13. DOI: 10.1007/s00439-003-1057-7. View

Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S . Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. 2005; 8(5):477-83. DOI: 10.1016/j.ejheart.2005.11.003. View

Li Z, Lilienbaum A, Butler-Browne G, Paulin D . Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development. Gene. 1989; 78(2):243-54. DOI: 10.1016/0378-1119(89)90227-8. View

Herrmann H, Strelkov S, Feja B, Rogers K, Brettel M, Lustig A . The intermediate filament protein consensus motif of helix 2B: its atomic structure and contribution to assembly. J Mol Biol. 2000; 298(5):817-32. DOI: 10.1006/jmbi.2000.3719. View

Vrabie A, Goldfarb L, Shatunov A, Nagele A, Fritz P, Kaczmarek I . The enlarging spectrum of desminopathies: new morphological findings, eastward geographic spread, novel exon 3 desmin mutation. Acta Neuropathol. 2005; 109(4):411-7. DOI: 10.1007/s00401-005-0980-1. View

Selcen D, Ohno K, Engel A . Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain. 2004; 127(Pt 2):439-51. DOI: 10.1093/brain/awh052. View

Fardeau M, GODET-GUILLAIN J, Tome F, Collin H, GAUDEAU S, Boffety C . [A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy (author's transl)]. Rev Neurol (Paris). 1978; 134(6-7):411-25. View

Luethje L, Boennemann C, Goldfarb L, Goebel H, Halle M . Prophylactic implantable cardioverter defibrillator placement in a sporadic desmin related myopathy and cardiomyopathy. Pacing Clin Electrophysiol. 2004; 27(4):559-60. DOI: 10.1111/j.1540-8159.2004.00484.x. View

10.

Lampe A, Bushby K . Collagen VI related muscle disorders. J Med Genet. 2005; 42(9):673-85. PMC: 1736127. DOI: 10.1136/jmg.2002.002311. View

11.

Li D, Tapscoft T, Gonzalez O, Burch P, Quinones M, Zoghbi W . Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999; 100(5):461-4. DOI: 10.1161/01.cir.100.5.461. View

12.

Miyamoto Y, Akita H, Shiga N, Takai E, Iwai C, Mizutani K . Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population. Eur Heart J. 2001; 22(24):2284-9. DOI: 10.1053/euhj.2001.2836. View

13.

Chang A, Potter J . Sarcomeric protein mutations in dilated cardiomyopathy. Heart Fail Rev. 2006; 10(3):225-35. DOI: 10.1007/s10741-005-5252-6. View

14.

Goudeau B, Rodrigues-Lima F, Fischer D, Casteras-Simon M, Sambuughin N, de Visser M . Variable pathogenic potentials of mutations located in the desmin alpha-helical domain. Hum Mutat. 2006; 27(9):906-13. DOI: 10.1002/humu.20351. View

15.

Fardeau M, Vicart P, Caron A, Chateau D, Chevallay M, Collin H . [Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material with mutation of the alphaB-cristallin gene]. Rev Neurol (Paris). 2000; 156(5):497-504. View

16.

Olive M, Goldfarb L, Shatunov A, Fischer D, Ferrer I . Myotilinopathy: refining the clinical and myopathological phenotype. Brain. 2005; 128(Pt 10):2315-26. DOI: 10.1093/brain/awh576. View

17.

Munoz-Marmol A, Strasser G, Isamat M, Coulombe P, Yang Y, Roca X . A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Natl Acad Sci U S A. 1998; 95(19):11312-7. PMC: 21639. DOI: 10.1073/pnas.95.19.11312. View

18.

Sjoberg G, Saavedra-Matiz C, Rosen D, Wijsman E, Borg K, Horowitz S . 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. 1999; 8(12):2191-8. DOI: 10.1093/hmg/8.12.2191. View

19.

Pou Serradell A, Lloreta Trull J, Corominas Torres J, Guicheney P . [Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material without mutation of the alphabeta-crystallin gene]. Neurologia. 2001; 16(5):195-203. View

20.

Dalakas M, Dagvadorj A, Goudeau B, Park K, Takeda K, Simon-Casteras M . Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. Neuromuscul Disord. 2003; 13(3):252-8. DOI: 10.1016/s0960-8966(02)00271-7. View