ISSN 2149-2263 | E-ISSN 2149-2271
The Anatolian Journal of Cardiology
The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye [Anatol J Cardiol]
Anatol J Cardiol. 2023; 27(11): 628-638 | DOI: 10.14744/AnatolJCardiol.2023.2805

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

Veysel Oktay1, Omaç Tüfekçioğlu2, Dilek Çicek  Yılmaz3, Ersel Onrat4, Dilay Karabulut5, Murat Çelik6, Akif Serhat Balcıoğlu7, Mehmet Murat  Sucu8, Güllü Özdemir9, Hakkı Kaya10, Mehmet Kış11, Barış Güven1, Oktay Bağdatoğlu12, Fatma Nihan  Turhan Çağlar5, Uygar Çağdaş  Yüksel6, İrfan Veysel  Düzen8, Ahmet Barutçu10, Özgüç Semih  Şimşir13, İbrahim Başarıcı14, Afşin Parspur15, Onur Dalgıç16, Fatma Özlem  Arıcan Özlük17, Mert Evlice18, Saim Sağ19, Muhammed Furkan  Deniz1, Arslan Öcal6, Emine Gazi10, Taner Şen15, Osman Özdabakoğlu19, Nermin Bayar Çakıcı20, Eren Ozan  Bakır21, Ayşegül Ülgen Kunak22, Gizem Çaylı13, Aybike Gül Taşdelen1, Ercan Akşit10, Şefika Uslu Çil13, Hüseyin Onay23
1Department of Cardiology, İstanbul University-Cerrahpaşa, Institute of Cardiology, İstanbul, Türkiye
2Clinic of Cardiology, Ankara City Hospital, Ankara, Türkiye
3Department of Cardiology, Faculty of Medicine, Mersin University, Mersin, Türkiye
4Department of Cardiology, Faculty of Medicine, Afyonkarahisar University of Health Sciences, Afyonkarahisar, Türkiye
5Clinic of Cardiology, Dr. Sadi Konuk Training and Research Hospital, İstanbul, Türkiye
6Department of Cardiology, University of Health Sciences, Gülhane Faculty of Medicine, Ankara, Türkiye
7Department of Cardiology, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Türkiye
8Department of Cardiology, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye
9Clinic of Cardiology, Private Çekirge Heart and Arrhythmia Hospital, Bursa, Türkiye
10Department of Cardiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye
11Department of Cardiology, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye
12Clinic of Nephrology, Ankara City Hospital, Ankara, Türkiye
13Medical Affairs Rare Diseases, Sanofi, İstanbul, Türkiye
14Department of Cardiology, Faculty of Medicine, Akdeniz University, Antalya, Türkiye
15Clinic of Cardiology, Kütahya University of Health Sciences, Evliya Çelebi Training and Research Hospital, Kütahya, Türkiye
16Clinic of Cardiology, Private Kardiya Cardiology Center, İzmir, Türkiye
17Clinic of Cardiology, Private Cardiology Office, Bursa, Türkiye
18Clinics of Cardiology, Adana City Hospital, Adana, Türkiye
19Clinic of Cardiology, Acıbadem Bursa Hospital, Bursa, Türkiye
20Department of Cardiology, Antalya Training and Research Hospital, Antalya, Türkiye
21Department of Cardiology, Faculty of Medicine, Celal Bayar University, Manisa, Türkiye
22Clinic of Cardiology, Private Medstar Topçular Hospital, Antalya, Türkiye
23Gene2Info Health Informatics, İstanbul, Türkiye;Multigen Genetic Diseases Diagnosis Center, İzmir, Türkiye

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.

Keywords: Hypertrophic cardiomyopathy, genetic mutation, Fabry disease, next-generation sequencing

Veysel Oktay, Omaç Tüfekçioğlu, Dilek Çicek  Yılmaz, Ersel Onrat, Dilay Karabulut, Murat Çelik, Akif Serhat Balcıoğlu, Mehmet Murat  Sucu, Güllü Özdemir, Hakkı Kaya, Mehmet Kış, Barış Güven, Oktay Bağdatoğlu, Fatma Nihan  Turhan Çağlar, Uygar Çağdaş  Yüksel, İrfan Veysel  Düzen, Ahmet Barutçu, Özgüç Semih  Şimşir, İbrahim Başarıcı, Afşin Parspur, Onur Dalgıç, Fatma Özlem  Arıcan Özlük, Mert Evlice, Saim Sağ, Muhammed Furkan  Deniz, Arslan Öcal, Emine Gazi, Taner Şen, Osman Özdabakoğlu, Nermin Bayar Çakıcı, Eren Ozan  Bakır, Ayşegül Ülgen Kunak, Gizem Çaylı, Aybike Gül Taşdelen, Ercan Akşit, Şefika Uslu Çil, Hüseyin Onay. The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye. Anatol J Cardiol. 2023; 27(11): 628-638

Corresponding Author: Veysel Oktay
Manuscript Language: English


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