VEYSEL OKTAY, OMAÇ TÜFEKÇİOĞLU, DİLEK ÇİCEK YILMAZ, ERSEL ONRAT, DİLAY KARABULUT, MURAT ÇELİK, AKİF SERHAT BALCIOĞLU, MEHMET MURAT SUCU, GÜLLÜ ÖZDEMİR, HAKKI KAYA, MEHMET KIŞ, BARIŞ GÜVEN, OKTAY BAĞDATOĞLU, FATMA NİHAN TURHAN ÇAĞLAR, UYGAR ÇAĞDAŞ YÜKSEL, İRFAN VEYSEL DÜZEN, AHMET BARUTÇU, ÖZGÜÇ SEMİH ŞİMŞİR, İBRAHİM BAŞARICI, AFŞİN PARSPUR, ONUR DALGIÇ, FATMA ÖZLEM ARICAN ÖZLÜK, MERT EVLİCE, SAİM SAĞ, MUHAMMED FURKAN DENİZ, ARSLAN ÖCAL, EMİNE GAZİ, TANER ŞEN, OSMAN ÖZDABAKOĞLU, NERMİN BAYAR ÇAKICI, EREN OZAN BAKIR, AYŞEGÜL ÜLGEN KUNAK, GİZEM ÇAYLI, AYBİKE GÜL TAŞDELEN, ERCAN AKŞİT, ŞEFİKA USLU ÇİL, HÜSEYİN ONAY
The Anatolian Journal of Cardiology - 2023;27(11):628-638
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.
