„ Short communication

Genotype-phenotype correlations in Polish patients with hypertrophic cardiomyopathy: Preliminary report

Tadeusz Osadnik12Anna Frycz-Kurek3Mateusz Lejawa1Martyna Fronczek14Justyna Małyszek-Tumidajewicz5Wioletta Szczurek-Wasilewicz3Karolina Macioł-Skurk3Mariusz Gąsior6Bożena Szyguła-Jurkiewicz6
1Department of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
22nd Department of Cardiology and Angiology, Silesian Center for Heart Diseases, Zabrze, Poland
33rd Department of Cardiology, Silesian Center for Heart Diseases, Zabrze, Poland
4Kardio-Med Silesia, Zabrze, Poland
5Department of Cardiac, Vascular and Endovascular Surgery and Transplantology in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, Zabrze, Poland
63rd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

Correspondence to:

Tadeusz Osadnik, MD, PhD,

Department of Pharmacology,

Faculty of Medical Sciences in Zabrze,

Medical University of Silesia in Katowice,

Jordana 38, 41–800 Zabrze,

phone: +48 32 272 26 83,

e-mail: tadeusz.osadnik@icloud.com

Copyright by the Author(s), 2022

DOI: 10.33963/KP.a2022.0052

Received: January 24, 2022

Accepted: February 17, 2022

Early publication date: February 17, 2022


Hypertrophic cardiomyopathy (HCM) is commonly defined by the presence of increased left ventricular (LV) wall thickness which cannot be explained by abnormal loading conditions such as arterial hypertension and/or aortic valve stenosis. The prevalence of HCM is 1:500, which makes it one of the most common genetic cardiological diseases [1]. According to the literature, the isolated form of HCM is most often caused by the occurrence of pathogenic variants in genes encoding sarcomere proteins. Until now around 1500 pathogenic variants in 11 genes encoding sarcomere proteins were identified [2]. In this report, we present the clinical characteristics and the results of genetic testing of HCM patients diagnosed and treated in the 3rd Department and Clinical Department of Cardiology, the Silesian Center for Heart Diseases.


Forty-eight consecutive patients with HCM were recruited during their routine follow-up visit in the 3rd Department of Cardiology, the Silesian Center for Heart Diseases in Zabrze. Blood for biochemical analyses was collected after 810 hours of fasting; additionally, blood for genetic analyses was secured and stored in –80°C. The family history of each patient was collected in detail. Two patients were excluded because the diagnosis of HCM was negatively verified. The HCM sudden cardiac death risk score (HCM SCD risk score) was calculated for all patients [1]. Information regarding genetic and bioinformatics analysis is presented in Supplementary material.

Statistical analyses

Fisher’s exact test was used for detection of differences between categorical variables, whilst the Kruskal-Wallis test was used for detection of differences between continuous variables. The Dunn test was used as a post hoc test for the Kruskal-Wallis test. Two-sided P-value <0.05 was considered statistically significant for all comparisons, except for the post-hoc test where the Bonferroni correction was used. Continuous variables were reported as medians and interquartile ranges, categorical variables were reported as counts and percentages. Statistical analyses were carried out in R software [3].

Results and Discussion

We were able to identify the pathogenic/likely pathogenic variants associated with the occurrence of HCM in 15 (32.6%) patients. We have also found 16 additional variants that were classified as VUS (variant of uncertain significance). Interestingly 7 (44%) of those variants were predicted to have a significant damaging effect on coded protein by both SIFT and PolyPhen-2 prediction algorithms (PolyPhen-2 score 0.74 and Sift score 0.04). There were no significant differences in clinical characteristics between the groups. There was, however, a trend toward a higher HCM SCD risk score in patients with pathogenic/likely pathogenic variants (Table 1).

Table 1. Clinical characteristics of the study population, and variants identified as disease-causing in the studied population

Pathogenic/likely pathogenic variant positive (n = 15)

Variant of uncertain significance (n = 16)

No identified pathogenic/VUS variant (n = 15)


Age, years, median (IQR)

51 (37–59)

58 (46–68)

55 (40–65)


Male gender, n (%)

9 (60)

8 (50)

9 (60)


Heart failure, n (%)

9 (60)

9 (56)

7 (47)


Alcohol ablation or myectomy of IVS, n (%)

1 (7)

3 (19)

2 (13)


Implantable cardioverter defibrillation, n (%)

6 (40)

5 (33)

5 (33)


Atrial fibrillation, n (%)

6 (40)

6 (38)

2 (13)


Ventricular tachycardia, n (%)

7 (47)

5 (31)

4 (27)


HCM-SCD risk score, median (IQR)

5.7 (4.5–9.4)

3.4 (2.1–7.1)

3.7 (2.3–5.4)


NT-proBNP, pg/ml, median (IQR)

906 (177–1651)

657 (404–1025)

349 (139– 959)


Max. thickness of LV, mm, median (IQR)

20 (17.5–21)

19.5 (16–21.3)

18.0 (15.5–21)


LVOT Vmax (Valsalva), mm Hg, median (IQR)

9 (5–68)

15 (6–63)

22 (10–43)


Identified pathogenic/likely pathogenic variants (n = 15)

Gene symbol

Gene name

Identified variants


Myosin-binding protein C

Transcript: NM_000256.3

c.3490+1G>Ta (2), c.3697C>Ta, c.821+1G>Aa, c.3040delCa, c.3407_3409delACTb, c.2449C>Tb (2×)


Myosin 7

Transcript: NM_000257.3

c.2555T>C1, c.5135G>Aa,



Essential myosin light chain 3

Transcript: NM_000258.2



Troponin I3

Transcript: NM_000363.5



Troponin T

Transcript: NM_000364.3



Ryanodine receptor 2

Transcript: NM_001035.2


HCM is one of the most common cardiomyopathies. Despite this, only in 40%–60% of patients, it is possible to identify the variant responsible for the disease [1]. The reason why it is not possible to identify causative variants in a large proportion of patients may be due to the involvement of other genes not yet identified as associated with HCM. Oligo- or even polygenic inheritance may be another cause. In rare cases, copy number variations, microdeletions, as well as incorrect classification of myocardial hypertrophy as HCM, may be the reason [4, 5].

The most common pathogenic/likely pathogenic variants responsible for the occurrence of HCM in our population were identified in genes encoding proteins of the sarcomere, in particular, MYBPC3 and MYH7. This is consistent with the results of genetic testing of HCM patients in other populations [2, 4]. Our data suggested a possible relationship between a higher risk of SCD assessed using the HCM SCD risk score [1, 6] in patients with a confirmed pathogenic variant. This may reflect observations from other cohorts that in patients with identified causative variant the disease tends to have a more aggressive course [5]. The frequency of alcohol ablation or surgical myectomy was similar in both groups. Similar results were reported by Loar et al. [5]. In general, genotype-phenotype correlations in patients with HCM are modest [7, 8]. Interestingly in one case, we found a variant in the RYR2 gene pathogenic for catecholaminergic ventricular tachycardia (CPVT) and not HCM. We did not find any other variants in this patient in genes typically associated with HCM. This patient was burdened with recurrent ventricular arrhythmias and his HCM-SCD risk score was calculated to be 24.7. In literature, RYR2 variants were reported as a possible rare cause of HCM [9, 10]. The pathogenic variant in this gene was also proved to be associated with the HCM phenotype in animal studies [11]. Nonetheless, this variant will be subjected to segregation analysis, and we will try to carry out whole-exome sequencing in this patient.


In the studied population, we identified variants that might be responsible for the phenotype in 33% of patients. Further analysis is required to assess the potential pathogenicity of identified VUS found in 35% of cases.

Supplementary material

Supplementary material is available at https://journals.viamedica.pl/kardiologia_polska.

Article information

Acknowledgments: This work was supported by an internal grant (KNW-1-124/N/8/0) from the Medical University of Silesia for statutory activity.

Ethical approval: The study was approved by the Bioethical Committee of the Medical University of Silesia (KNW/0022/KB1/102/18) and by the Bioethical Committee of the Chamber of Physicians (KBCz-0018/2015). The study was conducted according to the guidelines of the Declaration of Helsinki.

Conflict of interest: None declared.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.


  1. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014; 35(39): 27332779, doi: 10.1093/eurheartj/ehu284, indexed in Pubmed: 25173338.
  2. Pysz P, Rajtar-Salwa R, Smolka G, et al. Mavacamten a new disease-specific option for pharmacological treatment of symptomatic patients with hypertrophic cardiomyopathy. Kardiol Pol. 2021; 79(9): 949954, doi: 10.33963/KP.a2021.0064, indexed in Pubmed: 34268723.
  3. Team RC. R: A Language and Environment for Statistical Computing [Internet]. Vienna: R Foundation for Statistical Computing; 2019. Available online: https: //www.r-project.org/ (Access: January 2022).
  4. Sabater-Molina M, Pérez-Sánchez I, Hernández Del Rincón JP, et al. Genetics of hypertrophic cardiomyopathy: A review of current state. Clin Genet. 2018; 93(1): 314, doi: 10.1111/cge.13027, indexed in Pubmed: 28369730.
  5. Loar RW, Bos JM, Will ML, et al. Genotype-phenotype correlations of hypertrophic cardiomyopathy when diagnosed in children, adolescents, and young adults. Congenit Heart Dis. 2015; 10(6): 529536, doi: 10.1111/chd.12280, indexed in Pubmed: 26061417.
  6. Steriotis AK, Sharma S. Risk stratification in hypertrophic cardiomyopathy. Eur Cardiol. 2015; 10(1): 3136, doi: 10.15420/ecr.2015.10.01.31, indexed in Pubmed: 30310420.
  7. Kuusisto J. Genetics of hypertrophic cardiomyopathy: what is the next step? Heart. 2020; 106(17): 12911292, doi: 10.1136/heartjnl-2020-317043, indexed in Pubmed: 32546508.
  8. Teekakirikul P, Zhu W, Huang HC, et al. Hypertrophic cardiomyopathy: an overview of genetics and management. Biomolecules. 2019; 9(12), doi: 10.3390/biom9120878, indexed in Pubmed: 31888115.
  9. Fujino N, Ino H, Hayashi K, et al. et al.. A novel missense mutation in cardiac ryanodine receptor gene as a possible cause of hypertrophic cardiomyopathy: Evidence from familial analysis. Circulation. 2006; 114(18): II-165915.
  10. Landstrom AP, Ackerman MJ. Beyond the cardiac myofilament: hypertrophic cardiomyopathy- associated mutations in genes that encode calcium-handling proteins. Curr Mol Med. 2012; 12(5): 507518, doi: 10.2174/156652412800620020, indexed in Pubmed: 22515980.
  11. Alvarado FJ, Bos JM, Yuchi Z, et al. Cardiac hypertrophy and arrhythmia in mice induced by a mutation in ryanodine receptor 2. JCI Insight. 2019; 5, doi: 10.1172/jci.insight.126544, indexed in Pubmed: 30835254.


Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Sp. z o.o. VM Group Sp.k., ul. Świętokrzyska 73 , 80–180 Gdańsk, Poland

phone:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl