Anatolian Journal of Cardiology (Oct 2023)

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

  • 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

DOI
https://doi.org/10.14744/AnatolJCardiol.2023.2805
Journal volume & issue
Vol. 27, no. 11
pp. 628 – 638

Abstract

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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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