Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2023 Jul;191(7):1804-1813.
doi: 10.1002/ajmg.a.63205. Epub 2023 Apr 7.

Novel insights on GTPBP3-associated hypertrophic cardiomyopathy

Petya Angelova  1 , Vasil Velchev  2 , Nikolay Stoyanov  2 , Slavena Atemin  3 , Tihomir Todorov  3 , Ivan Tourtourikov  1   3 , Vanyo Mitev  1 , Albena Todorova  1
Affiliations
Case Reports

Novel insights on GTPBP3-associated hypertrophic cardiomyopathy

Petya Angelova et al. Am J Med Genet A. 2023 Jul.

Abstract

About 100 genes have been associated with cardiomyopathies with genotype-phenotype correlations often hard to establish. Genetic testing may help to confirm the genetic diagnosis and assess the risk of inheritance in the family. A 25-year old male with hypertrophic cardiomyopathy and fasciculoventricular accessory pathway was referred for genetic testing by his cardiologist. Targeted PRKAG2 screening and whole-exome sequencing were performed, followed by Sanger sequencing segregation analysis in the family. The PRKAG2 gene screening was negative. Whole-exome sequencing revealed the following four variants in the patient: c.181G>C (p.Ala61Pro) and c.1199C>T (p.Thr400Met) in the GTPBP3 gene, as well as c.752C>T (p.Thr251Ile) and c.1760C>T (p.Pro587Leu) in the POLG gene. Family segregation analysis showed that the patient's mother is a carrier of variant c.181G>C and the patient's paternal grandmother is a carrier of variant c.1199C>T in the GTPBP3 gene, which is in accordance with an autosomal recessive model of inheritance of the disease. Both variants in the POLG are found paternally inherited in the patient's healthy half-brother, thus are not considered disease-causing. GTPBP3 variants have been reported in patients with hypertrophic cardiomyopathy, associated with combined oxidative phosphorylation deficiency 23. These novel variants represent the probable cause of the observed clinical symptoms in the patient.

Keywords: GTPBP3; genetic testing; hypertrophic cardiomyopathy; whole-exome sequencing.

PubMed Disclaimer

References

REFERENCES

    1. Ackerman, M. J., Priori, S. G., Willems, S., Berul, C., Brugada, R., Calkins, H., Camm, A. J., Ellinor, P. T., Gollob, M., Hamilton, R., Hershberger, R. E., Judge, D. P., Le Marec, H., McKenna, W. J., Schulze-Bahr, E., Semsarian, C., Towbin, J. A., Watkins, H., Wilde, A., … Zipes, D. P. (2011). HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European heart rhythm association (EHRA). Heart Rhythm, 8(8), 1308-1339. https://doi.org/10.1016/j.hrthm.2011.05.020
    1. Akhtar, M., & Elliott, P. (2018). The genetics of hypertrophic cardiomyopathy. Global Cardiology Science and Practice, 12(3), 36. https://doi.org/10.21542/gcsp.2018.36
    1. Alston, C. L., Rocha, M. C., Lax, N. Z., Turnbull, D. M., & Taylor, R. W. (2017). The genetics and pathology of mitochondrial disease. The Journal of Pathology, 241(2), 236-250. https://doi.org/10.1002/path.4809
    1. Asano, K., Suzuki, T., Saito, A., Wei, F. Y., Ikeuchi, Y., Numata, T., Tanaka, R., Yamane, Y., Yamamoto, T., Goto, T., Kishita, Y., Murayama, K., Ohtake, A., Okazaki, Y., Tomizawa, K., Sakaguchi, Y., & Suzuki, T. (2018). Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. Nucleic Acids Research, 46(4), 1565-1583. https://doi.org/10.1093/nar/gky068
    1. Branzi, A., Romeo, G., Specchia, S., Lolli, C., Binetti, G., Devoto, M., Bacchi, M., & Magnani, B. (1985). Genetic heterogeneity of hypertrophic cardiomyopathy. International Journal of Cardiology, 7(2), 129-138. https://doi.org/10.1016/0167-5273(85)90352-3

Publication types

LinkOut - more resources