肥厚型心肌病是一种常见的遗传性心脏病,高达40%-60%的患者心脏肌节蛋白基因突变。这项遗传诊断研究旨在检测致病性或可能致病性肌节和非肌节基因突变,并确认诊断为肥厚型心肌病的患者的最终分子诊断。
在Türkiye的23个中心进行的这项全国性多中心研究中,共纳入了392例肥厚型心肌病患者。使用下一代测序技术用17基因肥厚型心肌病小组分析所有样品。基因组包括ACTC1、DES、FLNC,GLA,LAMP2,MYBPC3,MYH7,MYL2,MYL3,PLN,PRKAG2、PTPN11、TNNC1、TNNI3、TNNT2、TPM1和TTR基因。
下一代测序小组确定了阳性遗传变异(未知意义的变异,可能是致病性的或致病性的)在392份样本中的121份的12个基因中,包括30.4%(119/392)的测试样品中的肌节基因突变,0.5%(2/392)的样品中的半乳糖苷酶α变体和0.025%(1/392)的TTR变体。在121个阳性样品中的69个(57.0%)中鉴定出的可能的致病或致病变体产生了确认的分子诊断。肥厚型心肌病和肥厚型心肌病表型的诊断率为17.1%(肥厚型心肌病变异型为15.8%),法布里病的诊断率为0.5%。
我们的研究表明,基因突变的分布,法布里病的患病率,和TTR淀粉样变性在土耳其人群诊断为肥厚型心肌病与其他人群相似,但是肌节基因突变的百分比略低。
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.
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.
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.
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.