RESUMO
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.
Assuntos
Cardiomiopatia Hipertrófica , Doença de Fabry , Humanos , Sarcômeros/genética , Sarcômeros/metabolismo , Sarcômeros/patologia , Mutação , Cardiomiopatia Hipertrófica/genética , FenótipoRESUMO
Elevated cardiac troponin T (cTnT) has been associated with shorter survival in hemodialysis patients. Moreover, intravenous (IV) iron treatment has been held responsible for oxidative stress and accelerated atherosclerosis in these patients. In the present study, we investigated the relationship between cTnT concentration, IV iron treatment, and parameters of iron status. In addition, parameters of oxidative stress, inflammation, and atherosclerosis were evaluated. Predialysis blood samples of 78 chronic hemodialysis patients were analyzed for cTnT, malondialdehyde, creatine kinase (CK), and CK-isoenzyme MB (CK-MB). In addition, the mean value of predialysis serum samples collected during the last year, were considered for homocysteine, ferritin, iron, iron binding capacity, blood cell counts, blood urea nitrogen, creatinine, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, phosphate, iPTH, cholesterol, and triglyceride. The quantity of IV iron sucrose administered during the last two years was counted from the patients' files. Echocardiography, all events related to ischemic heart disease, and urine volume were also recorded. Elevated cTnT levels (> or =0.10 ng/mL) were found in 18 patients (23.1%). The amount of iron administered was 2264+/-1871 mg with a range 0-7000 mg. Patients with elevated cTnT levels received more IV iron than those with normal cTnT (3692+/-1771 vs. 1761+/-1595 mg, p<0.001). The serum ferritin level was higher in patients with elevated cTnT (median levels; 477 vs. 288 ng/mL; P<0.05). Patients with elevated cTnT were longer on dialysis compared to those with normal levels (median times; 35.5 vs. 15 months, P<0.01) and regression analysis identified the amount of administered iron as an independent factor for elevated cTnT (P<0.01). Intravenous iron treatment and high ferritin concentration are related to high cTnT level, which has previously been incriminated as a survival marker in hemodialysis patients.