Familial Dilated Cardiomyopathy Associated with Congenital Defects in the Setting of a Novel VCL Mutation (Lys815Arg) in Conjunction with a Known MYPBC3 Variant

Overview

Journal Cardiogenetics

Publisher MDPI

Specialty Cardiology & Vascular Diseases

Date 2013 Sep 25

PMID 24062880

Citations 10

Authors

Quinn S Wells

Natalie L Ausborn

Birgit H Funke

Jean P Pfotenhauer

Joseph L Fredi

Samantha Baxter

Thomas D Disalvo

Charles C Hong

Affiliations

Soon will be listed here.

Abstract

Idiopathic dilated cardiomyopathy (DCM) is a primary myocardial disorder characterized by ventricular chamber enlargement and systolic dysfunction. Twenty to fifty percent of idiopathic DCM cases are thought to have a genetic cause. Of more than 30 genes known to be associated with DCM, rare variants in the and genes have been reported in several cases of DCM. In this report, we describe a family with DCM and congenital abnormalities who carry a novel missense mutation in the gene. More severely affected family members also possess a second missense variant in , raising the possibility that this variant may be a disease modifier. Interestingly, many of the affected individuals also have congenital defects, including two with bicuspid aortic valve with aortic regurgitation. We discuss the implications of the family history and genetic information on management of at-risk individuals with aortic regurgitation.

Citing Articles

Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.

Micolonghi C, Perrone F, Fabiani M, Caroselli S, Savio C, Pizzuti A Int J Mol Sci. 2024; 25(18).

PMID: 39337275 PMC: 11431948. DOI: 10.3390/ijms25189787.

Resequencing the Yaroslavl cattle genomes reveals signatures of selection and a rare haplotype on BTA28 likely to be related to breed phenotypes.

Ruvinskiy D, Igoshin A, Yurchenko A, Ilina A, Larkin D Anim Genet. 2022; 53(5):680-684.

PMID: 35711120 PMC: 9541747. DOI: 10.1111/age.13230.

Understanding the molecular basis of cardiomyopathy.

Bang M, Bogomolovas J, Chen J Am J Physiol Heart Circ Physiol. 2021; 322(2):H181-H233.

PMID: 34797172 PMC: 8759964. DOI: 10.1152/ajpheart.00562.2021.

An interesting Mybpc3 heterozygous mutation associated with bicuspid aortic valve.

Zhao X, Hou C, Xiao T, Xie L, Li Y, Jia J Transl Pediatr. 2020; 9(5):610-618.

PMID: 33209723 PMC: 7658766. DOI: 10.21037/tp-20-81.

An assessment of the role of vinculin loss of function variants in inherited cardiomyopathy.

Hawley M, Almontashiri N, Biesecker L, Berger N, Chung W, Garcia J Hum Mutat. 2020; 41(9):1577-1587.

PMID: 32516855 PMC: 7714388. DOI: 10.1002/humu.24061.

References

Zemljic-Harpf A, Miller J, Henderson S, Wright A, Manso A, Elsherif L . Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy. Mol Cell Biol. 2007; 27(21):7522-37. PMC: 2169049. DOI: 10.1128/MCB.00728-07. View

Garg V, Muth A, Ransom J, Schluterman M, Barnes R, King I . Mutations in NOTCH1 cause aortic valve disease. Nature. 2005; 437(7056):270-4. DOI: 10.1038/nature03940. View

Kasper E, Agema W, Hutchins G, Deckers J, Hare J, Baughman K . The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol. 1994; 23(3):586-90. DOI: 10.1016/0735-1097(94)90740-4. View

Olson T, Illenberger S, Kishimoto N, Huttelmaier S, Keating M, Jockusch B . Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002; 105(4):431-7. DOI: 10.1161/hc0402.102930. View

Michels V, Moll P, Miller F, Tajik A, Chu J, Driscoll D . The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992; 326(2):77-82. DOI: 10.1056/NEJM199201093260201. View

Maeda M, Holder E, Lowes B, Valent S, Bies R . Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein metavinculin. Circulation. 1997; 95(1):17-20. DOI: 10.1161/01.cir.95.1.17. View

Vasile V, Ommen S, Edwards W, Ackerman M . A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006; 345(3):998-1003. DOI: 10.1016/j.bbrc.2006.04.151. View

Morales A, Painter T, Li R, Siegfried J, Li D, Norton N . Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy. Circulation. 2010; 121(20):2176-82. PMC: 2900861. DOI: 10.1161/CIRCULATIONAHA.109.931220. View

Cripe L, Andelfinger G, Martin L, Shooner K, Benson D . Bicuspid aortic valve is heritable. J Am Coll Cardiol. 2004; 44(1):138-43. DOI: 10.1016/j.jacc.2004.03.050. View

10.

Kryukov G, Pennacchio L, Sunyaev S . Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet. 2007; 80(4):727-39. PMC: 1852724. DOI: 10.1086/513473. View

11.

Moiseyeva E, Weller P, Zhidkova N, Corben E, Patel B, Jasinska I . Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter. J Biol Chem. 1993; 268(6):4318-25. View

12.

Zimmerman R, Cox S, Lakdawala N, Cirino A, Mancini-DiNardo D, Clark E . A novel custom resequencing array for dilated cardiomyopathy. Genet Med. 2010; 12(5):268-78. PMC: 3018746. DOI: 10.1097/GIM.0b013e3181d6f7c0. View

13.

Hershberger R, Norton N, Morales A, Li D, Siegfried J, Gonzalez-Quintana J . Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet. 2010; 3(2):155-61. PMC: 2908892. DOI: 10.1161/CIRCGENETICS.109.912345. View

14.

Huntington K, Hunter A, Chan K . A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve. J Am Coll Cardiol. 1997; 30(7):1809-12. DOI: 10.1016/s0735-1097(97)00372-0. View

15.

Koteliansky V, Ogryzko E, Zhidkova N, Weller P, Critchley D, Vancompernolle K . An additional exon in the human vinculin gene specifically encodes meta-vinculin-specific difference peptide. Cross-species comparison reveals variable and conserved motifs in the meta-vinculin insert. Eur J Biochem. 1992; 204(2):767-72. DOI: 10.1111/j.1432-1033.1992.tb16692.x. View

16.

Belkin A, Ornatsky O, Kabakov A, Glukhova M, Koteliansky V . Diversity of vinculin/meta-vinculin in human tissues and cultivated cells. Expression of muscle specific variants of vinculin in human aorta smooth muscle cells. J Biol Chem. 1988; 263(14):6631-5. View

17.

Vasile V, Will M, Ommen S, Edwards W, Olson T, Ackerman M . Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy. Mol Genet Metab. 2005; 87(2):169-74. DOI: 10.1016/j.ymgme.2005.08.006. View

18.

Maron B, Towbin J, Thiene G, Antzelevitch C, Corrado D, Arnett D . 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.... Circulation. 2006; 113(14):1807-16. DOI: 10.1161/CIRCULATIONAHA.106.174287. View

19.

Fatkin D, Otway R, Richmond Z . Genetics of dilated cardiomyopathy. Heart Fail Clin. 2010; 6(2):129-40. DOI: 10.1016/j.hfc.2009.11.003. View

20.

Ehlermann P, Weichenhan D, Zehelein J, Steen H, Pribe R, Zeller R . Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene. BMC Med Genet. 2008; 9:95. PMC: 2584029. DOI: 10.1186/1471-2350-9-95. View