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Multicenter Study
. 2023 Nov 1;27(11):628-638.
doi: 10.14744/AnatolJCardiol.2023.2805. Epub 2023 Jul 19.

The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye

Veysel Oktay  1 , Omaç Tüfekçioğlu  2 , Dilek Çicek Yılmaz  3 , Ersel Onrat  4 , Dilay Karabulut  5 , Murat Çelik  6 , Akif Serhat Balcıoğlu  7 , Mehmet Murat Sucu  8 , Güllü Özdemir  9 , Hakkı Kaya  10 , Mehmet Kış  11 , Barış Güven  1 , Oktay Bağdatoğlu  1 , Fatma Nihan Turhan Çağlar  5 , Uygar Çağdaş Yüksel  6 , İrfan Veysel Düzen  8 , Ahmet Barutçu  10 , Özgüç Semih Şimşir  12 , İbrahim Başarıcı  5 , Afşin Parspur  6 , Onur Dalgıç  8 , Fatma Özlem Arıcan Özlük  10 , Mert Evlice  13 , Saim Sağ  14 , Muhammed Furkan Deniz  1 , Arslan Öcal  6 , Emine Gazi  10 , Taner Şen  6 , Osman Özdabakoğlu  14 , Nermin Bayar Çakıcı  15 , Eren Ozan Bakır  16 , Ayşegül Ülgen Kunak  17 , Gizem Çaylı  12 , Aybike Gül Taşdelen  1 , Ercan Akşit  10 , Şefika Uslu Çil  12 , Hüseyin Onay  18
Affiliations
Multicenter Study

The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye

Veysel Oktay et al. Anatol J Cardiol. .

Abstract

Background: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy.

Methods: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes.

Results: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease.

Conclusions: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

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Conflict of interest statement

Declaration of Interests: Özgüç Semih Şimşir, MD, Gizem Çaylı, Pharm.D., and Şefika Uslu Çil, MD are employees of Sanofi Turkey. The other authors declare that they have no conflict of interest.

Figures

Figure 1.
Figure 1.
Percentage of positive variants overall and those with a molecular diagnosis.
Figure 2.
Figure 2.
The list of genes with positive variants overall and those with a molecular diagnosis.
See this image and copyright information in PMC

References

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