, 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 12
, Fatma Nihan Turhan Çağlar 5
, Uygar Çağdaş Yüksel 6
, İrfan Veysel Düzen 8
, Ahmet Barutçu 10
, Özgüç Semih Şimşir 13
, İbrahim Başarıcı 14
, Afşin Parspur 15
, Onur Dalgıç 16
, Fatma Özlem Arıcan Özlük 17
, Mert Evlice 18
, Saim Sağ 19
, Muhammed Furkan Deniz 1
, Arslan Öcal 6
, Emine Gazi 10
, Taner Şen 15
, Osman Özdabakoğlu 19
, Nermin Bayar Çakıcı 20
, Eren Ozan Bakır 21
, Ayşegül Ülgen Kunak 22
, Gizem Çaylı 13
, Aybike Gül Taşdelen 1
, Ercan Akşit 10
, Şefika Uslu Çil 13
, Hüseyin Onay 23
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
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.