A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy

Schirmer I, Dieding M, Klauke B, Brodehl A, Gärtner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H (2018)
Molecular Genetics & Genomic Medicine 6(2): 288-293.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ; ; ; ;
Abstract / Bemerkung
Background DES mutations cause different cardiac and skeletal myopathies. Most of them are missense mutations. Methods Using a next-generation sequencing cardiac 174 gene panel, we identified a novel heterozygous in-frame indel mutation (DES-c.493_520del28insGCGT, p.Q165_A174delinsAS) in a Caucasian patient with cardiomyopathy in combination with atrioventricular block and skeletal myopathy. This indel mutation is located in the coding region of the first exon. Family anamnesis revealed a history of sudden cardiac death. We performed cell transfection experiments and in vitro assembly experiments to prove the pathogenicity of this novel DES indel mutation. Results These experiments revealed a severe filament formation defect of mutant desmin supporting the pathogenicity. In addition, we labeled a skeletal muscle biopsy from the mutation carrier revealing cytoplasmic desmin positive protein aggregates. In summary, we identified and functionally characterized a pathogenic DES indel mutation causing cardiac and skeletal myopathy. Conclusion Our study has relevance for the clinical and genetic interpretation of further DES indel mutations causing cardiac or skeletal myopathies and might be helpful for risk stratification.
Erscheinungsjahr
Zeitschriftentitel
Molecular Genetics & Genomic Medicine
Band
6
Ausgabe
2
Seite(n)
288-293
ISSN
PUB-ID

Zitieren

Schirmer I, Dieding M, Klauke B, et al. A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine. 2018;6(2):288-293.
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., et al. (2018). A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine, 6(2), 288-293. doi:10.1002/mgg3.358
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., Schulz, U., Paluszkiewicz, L., Anselmetti, D., et al. (2018). A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine 6, 288-293.
Schirmer, I., et al., 2018. A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine, 6(2), p 288-293.
I. Schirmer, et al., “A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy”, Molecular Genetics & Genomic Medicine, vol. 6, 2018, pp. 288-293.
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., Schulz, U., Paluszkiewicz, L., Anselmetti, D., Milting, H.: A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine. 6, 288-293 (2018).
Schirmer, Ilona, Dieding, Mareike, Klauke, Bärbel, Brodehl, Andreas, Gärtner-Rommel, Anna, Walhorn, Volker, Gummert, Jan, Schulz, Uwe, Paluszkiewicz, Lech, Anselmetti, Dario, and Milting, Hendrik. “A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy”. Molecular Genetics & Genomic Medicine 6.2 (2018): 288-293.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Link(s) zu Volltext(en)
Access Level
OA Open Access

3 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Mutations in genes associated with either myopathy or noncompaction.
Finsterer J, Stollberger C., Herz (), 2018
PMID: 29679098
Molecular insights into cardiomyopathies associated with desmin (DES) mutations.
Brodehl A, Gaertner-Rommel A, Milting H., Biophys Rev 10(4), 2018
PMID: 29926427
Intermediate filaments in cardiomyopathy.
Tsikitis M, Galata Z, Mavroidis M, Psarras S, Capetanaki Y., Biophys Rev 10(4), 2018
PMID: 30027462

24 References

Daten bereitgestellt von Europe PubMed Central.

Desmin, desminopathy and the complexity of genetics.
Azzimato V, Genneback N, Tabish AM, Buyandelger B, Knoll R., J. Mol. Cell. Cardiol. 92(), 2016
PMID: 26807690
Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease.
Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A., Nat. Genet. 27(1), 2001
PMID: 11138011
Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect.
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., J. Mol. Cell. Cardiol. 91(), 2015
PMID: 26724190
Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy.
Brodehl A, Ferrier RA, Hamilton SJ, Greenway SC, Brundler MA, Yu W, Gibson WT, McKinnon ML, McGillivray B, Alvarez N, Giuffre M, Schwartzentruber J; FORGE Canada Consortium, Gerull B., Hum. Mutat. 37(3), 2016
PMID: 26666891
The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy.
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., Hum. Mutat. 38(8), 2017
PMID: 28493373
Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants.
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., J. Biol. Chem. 287(19), 2012
PMID: 22403400
Predicting the functional effect of amino acid substitutions and indels.
Choi Y, Sims GE, Murphy S, Miller JR, Chan AP., PLoS ONE 7(10), 2012
PMID: 23056405
HL‐1 cells: A cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte
AUTHOR UNKNOWN, 1998
Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease.
Goldfarb LG, Dalakas MC., J. Clin. Invest. 119(7), 2009
PMID: 19587455
Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks.
Koster S, Weitz DA, Goldman RD, Aebi U, Herrmann H., Curr. Opin. Cell Biol. 32(), 2015
PMID: 25621895
Crystal Structure of Vimentin (fragment 144‐251) from Homo sapiens, Northeast Structural Genomics Consortium Target HR4796B
AUTHOR UNKNOWN, 2011
New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses.
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., Acta Neuropathol Commun 4(), 2016
PMID: 26842778
C2C12 cells: biophysical, biochemical, and immunocytochemical properties.
McMahon DK, Anderson PA, Nassar R, Bunting JB, Saba Z, Oakeley AE, Malouf NN., Am. J. Physiol. 266(6 Pt 1), 1994
PMID: 8023908
A dysfunctional desmin mutation in a patient with severe generalized myopathy
AUTHOR UNKNOWN, 1998
GFAP and its role in Alexander disease.
Quinlan RA, Brenner M, Goldman JE, Messing A., Exp. Cell Res. 313(10), 2007
PMID: 17498694
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.
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; ACMG Laboratory Quality Assurance Committee., Genet. Med. 17(5), 2015
PMID: 25741868
Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.
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., J Interv Card Electrophysiol 28(2), 2010
PMID: 20390331
Mutation in BAG3 causes severe dominant childhood muscular dystrophy.
Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG., Ann. Neurol. 65(1), 2009
PMID: 19085932
Desmin-related myopathy.
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., Clin. Genet. 80(4), 2010
PMID: 20718792
Prevalence of desmin mutations in dilated cardiomyopathy.
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; Familial Cardiomyopathy Registry; BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank., Circulation 115(10), 2007
PMID: 17325244

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 29274115
PubMed | Europe PMC

Suchen in

Google Scholar