Kaniper Scott, Lynch Dorret, Owens Samuel M, Ibric Larisa, Vabishchevich Yuliya, Nyantakyi Nana, Chun Fan, Sam Lionel, Fabrizio Carly, Hamad Eman, Gerhard Glenn S
Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Department of Medicine, Section of Cardiology, Temple University Health System, Philadelphia, PA 19140, USA.
J Pers Med. 2024 Feb 29;14(3):271. doi: 10.3390/jpm14030271.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive systemic disease involving the extracellular deposition of misfolded transthyretin protein. The hereditary subtype is caused by mutations in the transthyretin ( gene. An estimated 2-3% of individuals of African American (AA) ancestry carry the p.Val142Ile (V142I, also referred to as V122I) pathogenic variant. The non-specific clinical nature of ATTR-CM makes it challenging to diagnose clinically, and the high allele frequency of V142I suggests that many patients with hereditary ATTR-CM may not have been tested. An analysis of electronic health record data from over 13,000 AA patients with a diagnostic code for heart disease or arrhythmia who also had additional amyloid-related findings were not diagnosed with amyloidosis at higher rates than those with heart failure or arrhythmia who did not have additional amyloid-related clinical diagnoses. Similarly, after genotyping 666 AA patients with heart failure or arrhythmia, V142I carriers appeared to be clinically indistinguishable based on amyloid-related non-cardiac diagnoses from those who did not carry the allele. No additional gene sequence variants were found in the wildtype V142V patients with heart failure or arrhythmia who had additional amyloid-related diagnoses. Genetic testing for ATTR-CM may be important for timely diagnosis.
转甲状腺素蛋白淀粉样心肌病（ATTR-CM）是一种进行性全身性疾病，涉及错误折叠的转甲状腺素蛋白在细胞外沉积。遗传性亚型由转甲状腺素蛋白（基因）突变引起。估计有2%-3%的非裔美国人（AA）携带p.Val142Ile（V142I，也称为V122I）致病变体。ATTR-CM的非特异性临床特征使其在临床诊断上具有挑战性，而V142I的高等位基因频率表明许多遗传性ATTR-CM患者可能未接受检测。对超过13000名患有心脏病或心律失常诊断代码且有其他淀粉样蛋白相关发现的AA患者的电子健康记录数据进行分析，发现他们被诊断为淀粉样变性的比例并不高于那些没有其他淀粉样蛋白相关临床诊断的心力衰竭或心律失常患者。同样，在对666名患有心力衰竭或心律失常的AA患者进行基因分型后，基于淀粉样蛋白相关的非心脏诊断，V142I携带者与未携带该等位基因的患者在临床上似乎没有区别。在患有心力衰竭或心律失常且有其他淀粉样蛋白相关诊断的野生型V142V患者中未发现其他基因序列变异。ATTR-CM的基因检测对于及时诊断可能很重要。
