Pathogenetics of Cardiomyopathy

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

This review summarizes the current state of knowledge on the genetic factors of both primary or Mendelian cardiomyopathies (CMPs) and some of its secondary forms. Dozens of genes with pathogenic/probably pathogenic variants have been described for primary CMPs. In most cases, the spectrum of causal genetic variants is specific for different CMPs, but shared genes and variants are also discovered. On the one hand genetic causes of diseases have not been established for all cases of primary CMPs, but on the other hand pathogenic variants in Mendelian disease genes are also found for its secondary forms. The genetic component in the development of both primary and secondary CMPs was also established during genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with both primary and secondary CMPs are in most cases specific for different types of disease and make a small contribution to an individual’s overall risk. The link between some SNPs and electro- or echocardiogram features of the normal heart has been reported in the population. Most of the CMPs-associated SNPs are localized in non-coding regions of the genome, but they have a regulatory potential, acting in the heart as loci that affect the level of expression (eQTL), splicing (sQTL) or epigenetic modifications. It is noteworthy that the effects of the eQTL and sQTL genotypes in some cases are not equivalent for different anatomical regions of the heart. The phenotype and clinical presentation of CMPs in general can be determined by a wide range of rare pathogenic/probably pathogenic variants with a strong effect and common polymorphisms with a small effect and modified by epigenetic factors.

About the authors

A. N. Kucher

Research Institute of Medical Genetics, Tomsk National Research Medical Center
of the Russian Academy of Sciences

Email: maria.nazarenko@medgenetics.ru
Russia, 634050, Tomsk

A. A. Sleptcov

Research Institute of Medical Genetics, Tomsk National Research Medical Center
of the Russian Academy of Sciences

Email: maria.nazarenko@medgenetics.ru
Russia, 634050, Tomsk

M. S. Nazarenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center
of the Russian Academy of Sciences

Author for correspondence.
Email: maria.nazarenko@medgenetics.ru
Russia, 634050, Tomsk

References

  1. McKenna W.J., Maron B.J., Thiene G. Classification, epidemiology, and global burden of cardiomyopathies // Circ. Res. 2017. V. 121. № 7. P. 722–730. https://doi.org/10.1161/CIRCRESAHA.117.309711
  2. Salemi V.M.C., Mohty D., Altavila S.L.L. et al. Insights into the classification of cardiomyopathies: past, present, and future directions // Clinics (Sao Paulo). 2021. V. 76. Р. e2808. https://doi.org/10.6061/clinics/2021/e2808
  3. McKenna W.J., Judge D.P. Epidemiology of the inherited cardiomyopathies // Nat. Rev. Cardiol. 2021. V. 18. № 1. P. 22–36. https://doi.org/10.1038/s41569-020-0428-2
  4. Ommen S.R., Mital S., Burke M.A. et al. AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines // Circulation. 2020. V. 142. Iss. 25. Р. e558–e631. https://doi.org/10.1161/CIR.0000000000000937
  5. Corrado D., Link M.S., Calkins H. Arrhythmogenic right ventricular cardiomyopathy // N. Engl. J. Med. 2017. V. 376. № 1. P. 61–72. https://doi.org/10.1056/NEJMra1509267
  6. Ciarambino T., Menna G., Sansone G., Giordano M. Cardiomyopathies: an overview // Int. J. Mol. Sci. 2021. V. 22. Iss. 14. https://doi.org/10.3390/ijms22147722
  7. Hey T.M., Rasmussen T.B., Madsen T. et al. Clinical and genetic investigations of 109 index patients with dilated cardiomyopathy and 445 of their relatives // Circ. Heart Fail. 2020. V. 13. № 10. Р. e006701. https://doi.org/10.1161/circheartfailure.119.006701
  8. Robertson J., Lindgren M., Schaufelberger M. et al. Body mass index in young women and risk of cardiomyopathy: A long-term follow-up study in Sweden // Circulation. 2020. V. 141. Iss. 7. P. 520–529. https://doi.org/10.1161/circulationaha.119.044056
  9. Peters S., Johnson R., Birch S. et al. Familial dilated cardiomyopathy // Heart Lung Circ. 2020. V. 29. Iss. 4. P. 566–574. https://doi.org/10.1016/j.hlc.2019.11.018
  10. Замараева Д.В., Трунина И.И., Котлукова Н.П. и др. Дебют генетически обусловленной дилатационной кардиомиопатии в исходе перенесенного миокардита (клинический случай) // Клин. и эксперим. хирургия. Журн. им. акад. Б.В. Петровского. 2020. Т. 8. № 3(29). С. 110–118. https://doi.org/10.33029/2308-1198-2020-8-3-110-118
  11. Povysil G., Chazara O., Carss K.J. et al. Assessing the role of rare genetic variation in patients with heart failure // JAMA Cardiol. 2021. V. 6. № 4. e206500. https://doi.org/10.1001/jamacardio.2020.6500
  12. Tiron C., Campuzano O., Fernández-Falgueras A. et al. Prevalence of pathogenic variants in cardiomyopathy-associated genes in myocarditis // Circ. Genom Precis. Med. 2022. V. 15. № 3. https://doi.org/10.1161/CIRCGEN.121.003408
  13. Patel A.P., Dron J.S., Wang M. et al. Association of pathogenic DNA variants predisposing to cardiomyopathy with cardiovascular disease outcomes and all-cause mortality // JAMA Cardiol. 2022. V. 7. № 7. P. 723–732. https://doi.org/10.1001/jamacardio.2022.0901
  14. Lazarte J., Jurgens S.J., Choi S.H. et al. LMNA variants and risk of adult-onset cardiac disease // J. Am. Coll. Cardiol. 2022. V. 80. № 1. P. 50–59. https://doi.org/10.1016/j.jacc.2022.04.035
  15. Cipriani A., Perazzolo Marra M., Bariani R. et al. Differential diagnosis of arrhythmogenic cardiomyopathy: phenocopies versus disease variants // Minerva Med. 2021. V. 112. № 2. P. 269–280. https://doi.org/10.23736/S0026-4806.20.06782-8
  16. Mattesi G., Cipriani A., Bauce B. et al. Arrhythmogenic left ventricular cardiomyopathy: Genotype-phenotype correlations and new diagnostic criteria // J. Clin. Med. 2021. V. 10. Iss. 10. https://doi.org/10.3390/jcm10102212
  17. Lee T.M., Hsu D.T., Kantor P. et al. Pediatric cardiomyopathies // Circ. Res. 2017. V. 21. № 7. P. 855–873. https://doi.org/10.1161/CIRCRESAHA.116.309386
  18. Лутохина Ю.А., Благова О.В., Шестак А.Г. и др. Сочетание аритмогенной дисплазии правого желудочка и некомпактного миокарда левого желудочка как особая форма кардиомиопатии: клиника, диагностика, генетическая природа, течение // Вестн. РАМН. 2020. Т. 75. № 6. С. 594–604. https://doi.org/10.15690/vramn1245
  19. Blagova O., Alieva I., Kogan E. et al. Mixed hypertrophic and dilated phenotype of cardiomyopathy in a patient with homozygous in-frame deletion in the MYBPC3 gene treated as myocarditis for a long time // Front. Pharmacol. 2020. V. 11. https://doi.org/10.3389/fphar.2020.579450
  20. Jefferies J.L., Wilkinson J.D., Sleeper L.A. et al. Cardiomyopathy phenotypes and outcomes for children with left ventricular myocardial noncompaction: results from the Pediatric Cardiomyopathy Registry // J. Card. Fail. 2015. V. 21. № 1. P. 877–884. https://doi.org/10.1016/j.cardfail.2015.06.381
  21. Webber S.A., Lipshultz S.E., Sleeper L.A. et al. Outcomes of restrictive cardiomyopathy in childhood and the influence of phenotype: A report from the Pediatric Cardiomyopathy Registry // Circulation. 2012. V. 126. Iss. 10. P. 1237–1244. https://doi.org/10.1161/CIRCULATIONAHA.112.104638
  22. Lipshultz S.E., Orav E.J., Wilkinson J.D. et al. Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: An analysis of data from the Pediatric Cardiomyopathy Registry // Lancet. 2013. V. 382. № 9908. P. 1889–1897. https://doi.org/10.1016/S0140-6736(13)61685-2
  23. Кучер А.Н., Валиахметов Н.Р., Салахов Р.Р. и др. Фенотипическая вариабельность гипертрофической кардиомиопатии у носителей патогенного варианта p.Arg870His гена MYH7 // Бюл. сиб. медицины. 2022. Т. 21. № 3. С. 205–216. https://doi.org/10.20528/1682-0363-2022-3-205-216
  24. Кучер А.Н., Слепцов А.А., Назаренко М.С. Генетический ландшафт дилатационной кардиомиопатии // Генетика. 2022. Т. 58. № 4. С. 371–387. https://doi.org/10.31857/S0016675822030080
  25. Menon S.C., Michels V.V., Pellikka P.A. et al. Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology // Clin. Genet. 2008. V. 74. Iss. 5. P. 445–454. https://doi.org/10.1111/j.1399-0004.2008.01062.x
  26. Norrish G., Cleary A., Field E. et al. Clinical features and natural history of preadolescent nonsyndromic hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. 2022. V. 79. № 20. P. 1986–1997. https://doi.org/10.1016/j.jacc.2022.03.347
  27. Wu W., Lu C.X., Wang Y.N. et al. Novel phenotype–genotype correlations of restrictive cardiomyopathy with myosin-binding protein c (MYBPC3) gene mutations tested by next-generation sequencing // J. Am. Heart Assoc. 2015. V. 4. № 7.https://doi.org/10.1161/JAHA.115.001879
  28. Курушко Т.В., Вайханская Т.Г., Булгак А.Г. и др. Ламин A/C ассоциированная дилатационная кардиомиопатия: вариабельность клинических проявлений // Кардиология в Беларуси. 2018. Т. 10. № 6. С. 892–903.
  29. Simple ClinVar [Electronic resource]. URL: https://simple-clinvar.broadinstitute.org/. Accessed 03.2022.
  30. Pérez-Palma E., Gramm M., Nürnberg P. et al. Simple ClinVar: An interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database // Nucl. Acids Res. 2019. V. 47. № W1. P. W99–W105. https://doi.org/10.1093/nar/gkz411
  31. Salman O.F., El-Rayess H.M., Abi Khalil C. et al. Inherited cardiomyopathies and the role of mutations in non-coding regions of the genome // Front. Cardiovasc. Med. 2018. V. 5. № 77. https://doi.org/10.3389/fcvm.2018.00077
  32. Комиссарова С.М., Чакова Н.Н., Ниязова С.С. Гипертрофическая кардиомиопатия: анализ связи генотипа и фенотипа у пациентов с высоким риском внезапной смерти // Мед. генетика. 2018. Т. 17. № 11. С. 34–42.
  33. Walsh R., Offerhaus J.A., Tadros R., Bezzina C.R. Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies // Nat. Rev. Cardiol. 2022. V. 9. № 3. P. 151–167. https://doi.org/10.1038/s41569-021-00608-2
  34. Ingles J., Goldstein J., Thaxton C. et al. Evaluating the clinical validity of hypertrophic cardiomyopathy genes // Circ. Genom. Precis. Med. 2019. V. 12. № 2. https://doi.org/10.1161/CIRCGEN.119.002460
  35. Zigova M., Bernasovska J., Boronova I. et al. Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients // J. Clin. Lab. Anal. 2018. V. 32. № 3. https://doi.org/10.1002/jcla.22303
  36. Richmond C.M., James P.A., Pantaleo S. et al. Clinical and laboratory reporting impact of ACMG-AMP and modified ClinGen variant classification frameworks in MYH7-related cardiomyopathy // Genet. Med. 2021. V. 23. Iss. 6. P. 1108–1115. https://doi.org/10.1038/s41436-021-01107-y
  37. Kubo T., Gimeno J.R., Bahl A. et al. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype // J. Am. Coll. Cardiol. 2007. V. 49. № 25. P. 2419–2426. https://doi.org/10.1016/j.jacc.2007.02.061
  38. Vio R., Angelini A., Basso C. et al. Hypertrophic cardiomyopathy and primary restrictive cardiomyopathy: similarities, differences and phenocopies // J. Clin. Med. 2021. V. 10. № 9. Article 1954. https://doi.org/10.3390/jcm10091954
  39. Li S., Wu B., Yin G. et al. MRI characteristics, prevalence, and outcomes of hypertrophic cardiomyopathy with restrictive phenotype // Radiol. Cardiothorac. Imaging. 2020. V. 2. № 4. Р. e190158. https://doi.org/10.1148/ryct.2020190158
  40. Hershberger R.E., Jordan E. Dilated Cardiomyopathy Overview. 2007 Jul 27 [updated 2022 Apr 7] // Gene-Reviews® [Internet] / Eds Adam M.P., Ardinger H.H., Pagon R.A. et al. Seattle (WA): Univ. Washington, Seattle, 1993–2022.
  41. Towbin J.A., McKenna W.J., Abrams D.J. et al. HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy // Heart Rhythm. 2019. V. 16. № 11. P. e301–e372. https://doi.org/10.1016/j.hrthm.2019.05.007
  42. Groeneweg J.A., Bhonsale A., James C.A. et al. Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members // Circ. Cardiovasc. Genet. 2015. V. 8. № 3. P. 437–446. https://doi.org/10.1161/CIRCGENETICS.114.001003
  43. Pugh T.J., Kelly M.A., Gowrisankar S. et al. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing // Genet. Med. 2014. V. 16. Iss. 8. P. 601–608. https://doi.org/10.1038/gim.2013.204
  44. Jordan E., Hershberger R.E. Considering complexity in the genetic evaluation of dilated cardiomyopathy // Heart. 2021. V. 107. № 2. P. 106–112. https://doi.org/10.1136/heartjnl-2020-316658
  45. Morales A., Kinnamon D.D., Jordan E. et al. Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study // Circ. Genom. Precis. Med. 2020. V. 13. № 2. https://doi.org/10.1161/CIRCGEN.119.002480
  46. Lopes L.R., Zekavati A., Syrris P. et al. Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing // J. Med. Genet. 2013. V. 50. № 4. P. 228–239. https://doi.org/10.1136/jmedgenet-2012-101270
  47. Tran Vu M.T., Nguyen T.V., Huynh N.V. et al. Presence of hypertrophic cardiomyopathy related gene mutations and clinical manifestations in Vietnamese patients with hypertrophic cardiomyopathy // Circ. J. 2019. V. 83. № 9. P. 1908–1916. https://doi.org/10.1253/circj.CJ-19-0190
  48. Harper A.R., Goel A., Grace C. et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity // Nat. Genet. 2021. V. 53. № 2. P. 135–142. https://doi.org/10.1038/s41588-020-00764-0
  49. Villard E., Perret C., Gary F. et al. A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy // Eur. Heart J. 2011. V. 32. Iss. 9. P. 1065–1076. https://doi.org/10.1093/eurheartj/ehr105
  50. Meder B., Rühle F., Weis T. et al. A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy // Eur. Heart J. 2014. V. 35. Iss. 16. P. 1069–1077. https://doi.org/10.1093/eurheartj/eht251
  51. Xu H., Dorn G.W. 2nd, Shetty A. et al. A Genome-wide association study of idiopathic dilated cardiomyopathy in African Americans // J. Pers. Med. 2018. V. 8. № 1. Article 11. https://doi.org/10.3390/jpm8010011
  52. de Denus S., Mottet F., Korol S. et al. A genetic association study of heart failure: More evidence for the role of BAG3 in idiopathic dilated cardiomyopathy // ESC Heart Fail. 2020. V. 7. № 6. P. 4384–4389. https://doi.org/10.1002/ehf2.12934
  53. Garnier S., Harakalova M., Weiss S. et al. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23 // Eur. Heart J. 2021. V. 42. Iss. 20. P. 2000–2011. https://doi.org/10.1093/eurheartj/ehab030
  54. Deng X., Sabino E.C., Cunha-Neto E. et al. Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects // PLoS One. 2013. V. 8. № 11. Р. e79629. https://doi.org/10.1371/journal.pone.0079629
  55. Casares-Marfil D., Strauss M., Bosch-Nicolau P. et al. A genome-wide association study identifies novel susceptibility loci in chronic chagas cardiomyopathy // Clin. Infect. Dis. 2021. V. 73. № 4. P. 672–679. https://doi.org/10.1093/cid/ciab090
  56. Eitel I., Moeller C., Munz M. et al. Genome-wide association study in takotsubo syndrome – Preliminary results and future directions // Int. J. Cardiol. 2017. V. 236. P. 335–339. https://doi.org/10.1016/j.ijcard.2017.01.093
  57. López-Mejías R., Carmona F.D., Genre F. et al. Identification of a 3'-untranslated genetic variant of RARB associated with carotid intima-media thickness in rheumatoid arthritis: A Genome-Wide Association Study // Arthritis Rheumatol. 2019. V. 71. № 3. P. 351–360. https://doi.org/10.1002/art.40734
  58. Wang X., Sun C.L., Quiñones-Lombraña A. et al. CELF4 variant and anthracycline-related cardiomyopathy: A Children’s Oncology Group Genome-Wide Association Study // J. Clin. Oncol. 2016. V. 34. Iss. 8. P. 863–870. https://doi.org/10.1200/JCO.2015.63.4550
  59. Horne B.D., Rasmusson K.D., Alharethi R. et al. Genome-wide significance and replication of the chromosome 12p11.22 locus near the PTHLH gene for peripartum cardiomyopathy // Circ. Cardiovasc. Genet. 2011. V. 4. № 4. P. 359–366. https://doi.org/10.1161/CIRCGENETICS.110.959205
  60. GWAS Catalog [Electronic resource]. URL: https://www.ebi.ac.uk/gwas/. Accessed 05.2022.
  61. Tadros R., Francis C., Xu X. et al. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect // Nat. Genet. 2021. V. 53. № 2. P. 128–134. https://doi.org/10.1038/s41588-020-00762-2
  62. UCSC Genome Browser on Human (GRCh38/hg38) https://genome.ucsc.edu/.
  63. VannoPortal Index [Electronic resource]. URL: http://www.mulinlab.org/vportal/index.html/. Accessed 05.2022.
  64. National Center for Biotechnology Information Electronic resource]. URL: https://www.ncbi.nlm.nih.gov/. Accessed 06.2022.
  65. Genotype-Tissue Expression (GTEx) Portal [Electronic resource]. URL: https://gtexportal.org/home/. Accessed 06.2022.
  66. Ahn J., Wu H., Lee K. Integrative analysis revealing human heart-specific genes and consolidating heart-related phenotypes // Front Genet. 2020. V. 11.https://doi.org/10.3389/fgene.2020.00777
  67. Hammond C.M., Bao H., Hendriks I.A. et al. DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network // Mol. Cell. 2021. V. 81. № 12. P. 2533–2548.e9. https://doi.org/10.1016/j.molcel.2021.03.041
  68. Кучер А.Н., Назаренко М.С. Регуляторный потенциал ко-локализованных с генами кардиомиопатий некодирующих РНК // Генетика. 2023. Т. 59. № 4. С. 381–402.
  69. Кучер А.Н., Назаренко М.С. Эпигенетика кардиомиопатий: модификации гистонов и метилирование ДНК // Генетика. 2023. Т. 59. № 3. С. 266–282.
  70. Scolari F.L., Faganello L.S., Garbin H.I. et al. A systematic review of microRNAs in patients with hypertrophic cardiomyopathy // Int. J. Cardiol. 2021. V. 327. P. 146–154. https://doi.org/10.1016/j.ijcard.2020.11.004
  71. Gao J., Collyer J., Wang M. et al. Genetic dissection of hypertrophic cardiomyopathy with myocardial RNA-Seq // Int. J. Mol. Sci. 2020. V. 21. № 9. https://doi.org/10.3390/ijms21093040
  72. Huang G., Liu J., Yang C. et al. RNA sequencing discloses the genome wide profile of long noncoding RNAs in dilated cardiomyopathy // Mol. Med. Rep. 2019. V. 19. № 4. P. 2569–2580. https://doi.org/10.3892/mmr.2019.9937
  73. Hailu F.T., Karimpour-Fard A., Toni L.S. et al. Integrated analysis of miRNA-mRNA interaction in pediatric dilated cardiomyopathy // Pediatr. Res. 2022. V. 92. № 1. P. 98–108. https://doi.org/10.1038/s41390-021-01548-w
  74. Ensembl Genome Browser [Electronic resource]. URL: https://www.ensembl.org/index.html/. Accessed 06.2022.
  75. Su X., Lv L., Li Y. et al. lncRNA MIRF promotes cardiac apoptosis through the miR-26a-Bak1 axis // Mol. Ther. Nucl. Acids. 2020. V. 20. P. 841–850. https://doi.org/10.1016/j.omtn.2020.05.002
  76. Liu Y., Liu N., Bai F., Liu Q. Identifying ceRNA networks associated with the susceptibility and persistence of atrial fibrillation through weighted gene co-expression network analysis // Front. Genet. 2021. V. 12. https://doi.org/10.3389/fgene.2021.653474
  77. Esslinger U., Garnier S., Korniat A. et al. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy // PLoS One. 2017. V. 12. № 3. https://doi.org/10.1371/journal.pone.0172995
  78. Ochoa J.P., Sabater-Molina M., García-Pinilla J.M. et al. Formin homology 2 domain containing 3 (FHOD3) is a genetic basis for hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. 2018. V. 72. № 20. P. 2457–2467. https://doi.org/10.1016/j.jacc.2018.10.001
  79. Wu G., Ruan J., Liu J. et al. Variant spectrum of formin homology 2 domain-containing 3 gene in Chinese patients with hypertrophic cardiomyopathy // J. Am. Heart Assoc. 2021. V. 10. № 5. https://doi.org/10.1161/JAHA.120.018236
  80. Fernlund E., Kissopoulou A., Green H. et al. Hereditary hypertrophic cardiomyopathy in children and young adults – the value of reevaluating and expanding gene panel analyses // Genes (Basel). 2020. V. 11. № 12. https://doi.org/10.3390/genes11121472
  81. Qin X., Li P., Qu H.Q. et al. FLNC and MYLK2 gene mutations in a Chinese family with different phenotypes of cardiomyopathy // Int. Heart J. 2021. V. 62. № 1. P. 127–134. https://doi.org/10.1536/ihj.20-351
  82. Brun F., Gigli M., Graw S.L. et al. FLNC truncations cause arrhythmogenic right ventricular cardiomyopathy // J. Med. Genet. 2020. V. 57. № 4. P. 254–257. https://doi.org/10.1136/jmedgenet-2019-106394
  83. Xiao F., Wei Q., Wu B. et al. Clinical exome sequencing revealed that FLNC variants contribute to the early diagnosis of cardiomyopathies in infant patients // Transl. Pediatr. 2020. V. 9. № 1. P. 21–33. https://doi.org/10.21037/tp.2019.12.02
  84. Phelan D.G., Anderson D.J., Howden S.E. et al. ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy // Eur. Heart J. 2016. V. 37. Iss. 33. P. 2586–2590. https://doi.org/10.1093/eurheartj/ehw160
  85. Herkert J.C., Verhagen J.M.A., Yotti R. et al. Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants // Am. Heart. J. 2020. V. 225. P. 108–119. https://doi.org/10.1016/j.ahj.2020.03.023
  86. Lopes L.R., Garcia-Hernández S., Lorenzini M. et al. Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy // Eur. Heart J. 2021. V. 42. Iss. 32. P. 3063–3073. https://doi.org/10.1093/eurheartj/ehab424
  87. Wooten E.C., Hebl V.B., Wolf M.J. et al. Formin homology 2 domain containing 3 variants associated with hypertrophic cardiomyopathy // Circ. Cardiovasc. Genet. 2013. V. 6. № 1. P. 10–18. https://doi.org/10.1161/CIRCGENETICS.112.965277
  88. Kan-O M., Takeya R., Abe T. et al. Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis // Biol. Open. 2012. V. 1. № 9. P. 889–896. https://doi.org/10.1242/bio.20121370
  89. Fujimoto N., Kan-O M., Ushijima T. et al. Transgenic expression of the formin protein Fhod3 selectively in the embryonic heart: Role of actin-binding activity of Fhod3 and its sarcomeric localization during myofibrillogenesis // PLoS One. 2016. V. 11. № 2.https://doi.org/10.1371/journal.pone.0148472
  90. Ushijima T., Fujimoto N., Matsuyama S. et al. The actin-organizing formin protein Fhod3 is required for postnatal development and functional maintenance of the adult heart in mice // J. Biol. Chem. 2018. V. 293. Iss. 1. P. 148–162. https://doi.org/10.1074/jbc.M117.813931
  91. Matsuyama S., Kage Y., Fujimoto N. et al. Interaction between cardiac myosin-binding protein C and formin Fhod3 // Proc. Natl Acad. Sci. USA. 2018. V. 115. Iss. 19. P. E4386–E4395. https://doi.org/10.1073/pnas.1716498115
  92. Arimura T., Takeya R., Ishikawa T. et al. Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor // Circ. J. 2013. V. 77. № 12. P. 2990–2996. https://doi.org/10.1253/circj.cj-13-0255
  93. Myasnikov R., Bukaeva A., Kulikova O. et al. A case of severe left-ventricular noncompaction associated with splicing altering variant in the FHOD3 gene // Genes (Basel). 2022. V. 13. № 2. https://doi.org/10.3390/genes13020309
  94. Antoku S., Wu W., Joseph L.C. et al. ERK1/2 phosphorylation of FHOD connects signaling and nuclear positioning alternations in cardiac laminopathy // Dev. Cell. 2019. V. 51. № 5. P. 602–616.e12. https://doi.org/10.1016/j.devcel.2019.10.023
  95. Verdonschot J.A.J., Vanhoutte E.K., Claes G.R.F. et al. A mutation update for the FLNC gene in myopathies and cardiomyopathies // Hum. Mutat. 2020. V. 41. Iss. 6. P. 1091–1111. https://doi.org/10.1002/humu.24004
  96. Ortiz-Genga M.F., Cuenca S., Dal Ferro M. et al. Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies // J. Am. Coll. Cardiol. 2016. V. 68. № 22. P. 2440–2451. https://doi.org/10.1016/j.jacc.2016.09.927
  97. Begay R.L., Tharp C.A., Martin A. et al. FLNC gene splice mutations cause dilated cardiomyopathy // JACC Basic Transl. Sci. 2016. V. 1. № 5. P. 344–359. https://doi.org/10.1016/j.jacbts.2016.05.004
  98. Hall C.L., Gurha P., Sabater-Molina M. et al. RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy // Int. J. Cardiol. 2020. V. 302. P. 124–130. https://doi.org/10.1016/j.ijcard.2019.12.002
  99. Goli R., Li J., Brandimarto J. et al. Genetic and phenotypic landscape of peripartum cardiomyopathy // Circulation. 2021. V. 143. Iss. 19. P. 1852–1862. https://doi.org/10.1161/CIRCULATIONAHA.120. 052395
  100. Ito S., Asakura M., Liao Y. et al. Identification of the Mtus1 splice variant as a novel inhibitory factor against cardiac hypertrophy // J. Am. Heart Assoc. 2016. V. 5. № 7. https://doi.org/10.1161/JAHA.116.003521
  101. Parvatiyar M.S., Brownstein A.J., Kanashiro-Takeuchi R.M. et al. Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy // JCI Insight. 2019. V. 5. № 11. https://doi.org/10.1172/jci.insight.123855
  102. Stark K., Esslinger U.B., Reinhard W. et al. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy // PLoS Genet. 2010. V. 6. № 10. https://doi.org/10.1371/journal.pgen.1001167
  103. Стрельцова А.А., Гудкова А.Я., Полякова А.А. и др. Полиморфный вариант rs1739843 гена белка теплового шока 7 (HSPB7) и его связь с вариантами клинического течения и исходами у пациентов с гипертрофической кардиомиопатией (результаты 10-летнего наблюдения) // Рос. кардиол. журн. 2019. № 10. С. 7–15. https://doi.org/10.15829/1560-4071-2019-10-7-15
  104. Clausen A.G., Vad O.B., Andersen J.H., Olesen M.S. Loss-of-function variants in the SYNPO2L gene are associated with atrial fibrillation // Front. Cardiovasc. Med. 2021. V. 8. Article 650667. https://doi.org/10.3389/fcvm.2021.650667
  105. Hsu J., Gore-Panter S., Tchou G. et al. Genetic control of left atrial gene expression yields insights into the genetic susceptibility for atrial fibrillation // Circ. Genom Precis. Med. 2018. V. 11. № 3. https://doi.org/10.1161/CIRCGEN.118.002107
  106. Ma X., Mo C., Huang L. et al. An robust rank aggregation and least absolute shrinkage and selection operator analysis of novel gene signatures in dilated cardiomyopathy // Front. Cardiovasc. Med. 2021. V. 8. https://doi.org/10.3389/fcvm.2021.747803
  107. Aragam K.G., Chaffin M., Levinson R.T. et al. Phenotypic refinement of heart failure in a national biobank facilitates genetic discovery // Circulation. 2019. V. 139. P. 489–501. https://doi.org/10.1161/CIRCULATIONAHA.118.0-35774
  108. Celeghin R., Cipriani A., Bariani R. et al. Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death // Heart Rhythm. 2022. V. 19. № 2. P. 235–243. https://doi.org/10.1016/j.hrthm.2021.09.029
  109. Finocchiaro G., Merlo M., Sheikh N. et al. The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy // Eur. J. Heart Fail. 2020. V. 22. Iss. 7. P. 1097–1107. https://doi.org/10.1002/ejhf.1815
  110. Lee Y., Choi B., Lee M.S. et al. An artificial intelligence electrocardiogram analysis for detecting cardiomyopathy in the peripartum period // Int. J. Cardiol. 2022. V. 352. P. 72–77. https://doi.org/10.1016/j.ijcard.2022.01.064
  111. Yoneda Z.T., Anderson K.C., Quintana J.A. et al. Early-onset atrial fibrillation and the prevalence of rare variants in cardiomyopathy and arrhythmia genes // JAMA Cardiol. 2021. V. 6. № 12. P. 1371–1379. https://doi.org/10.1001/jamacardio.2021.3370
  112. Verweij N., Benjamins J.W., Morley M.P. et al. The genetic makeup of the electrocardiogram // Cell Syst. 2020. V. 11. Iss. 3. P. 229–238.e5. https://doi.org/10.1016/j.cels.2020.08.005
  113. Weng L.C., Hall A.W., Choi S.H. et al. Genetic determinants of electrocardiographic P-wave duration and relation to atrial fibrillation // Circ. Genom. Precis. Med. 2020. V. 13. № 5. P. 387–395. https://doi.org/10.1161/CIRCGEN.119.002874
  114. Liao W.C., Juo L.Y., Shih Y.L. et al. HSPB7 prevents cardiac conduction system defect through maintaining intercalated disc integrity // PLoS Genet. 2017. V. 13. № 8. https://doi.org/10.1371/journal.pgen.1006984
  115. Ke L., Meijering R.A., Hoogstra-Berends F. et al. HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in tachypaced atrial myocytes // PLoS One. 2011. V. 6. № 6.https://doi.org/10.1371/journal.pone.0020395
  116. Adriaens M.E., Lodder E.M., Moreno-Moral A. et al. Systems genetics approaches in rat identify novel genes and gene networks associated with cardiac conduction // J. Am. Heart Assoc. 2018. V. 7. № 21. https://doi.org/10.1161/JAHA.118.009243
  117. Pirruccello J.P., Bick A., Wang M. et al. Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy // Nat. Commun. 2020. V. 11. № 1. Article 2254. https://doi.org/10.1038/s41467-020-15823-7
  118. Biddinger K.J., Jurgens S.J., Maamari D. et al. Rare and common genetic variation underlying the risk of hypertrophic cardiomyopathy in a National Biobank // JAMA Cardiol. 2022. V. 7. № 7. P. 715–722. https://doi.org/10.1001/jamacardio.2022.1061
  119. Marian A.J. Oligogenic cardiomyopathy // J. Cardiovasc. Aging. 2022. V. 2. Article 3. https://doi.org/10.20517/jca.2021.27
  120. Pourebrahim K., Marian J.G., Tan Y. et al. A combinatorial oligogenic basis for the phenotypic plasticity between late-onset dilated and arrhythmogenic cardiomyopathy in a single family // J. Cardiovasc. Aging. 2021. V. 1. Article 12. https://doi.org/10.20517/jca.2021.15
  121. Баулина Н.М., Киселёв И.С., Чумакова О.С., Фаворова О.О. Гипертрофическая кардиомиопатия как олигогенное заболевание: аргументы транскриптомики // Мол. биология. 2020. Т. 54. № 6. С. 955–967. https://doi.org/10.31857/S0026898420060026
  122. Alimohamed M.Z., Johansson L.F., Posafalvi A. et al. Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients // Int. J. Cardiol. 2021. V. 332. P. 99–104. https://doi.org/10.1016/j.ijcard.2021.02.069

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2.

Download (1MB)
Indexing metadata

Copyright (c) 2023 А.Н. Кучер, А.А. Слепцов, М.С. Назаренко

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies