Liu Jason Y, Sara Afrida, Liu Jar-Yee, Fan Judith, Gupta Pritha, Wang Jessica
Department of Medicine, Geffen School of Medicine, University of California, 10833 Le Conte Avenue Los Angeles, CA, USA.
Clinical and Translational Science Institute, Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Eur Heart J Case Rep. 2018 Oct 22;2(4):yty108. doi: 10.1093/ehjcr/yty108. eCollection 2018 Dec.
Approximately 4% of the African-American population possess a valine-to-isoleucine (V122I) substitution within the transthyretin protein that results in a tendency for a normally tetrameric protein to dissociate into misfolded, monomeric subunits. These misfolded proteins can then accumulate pathologically and cause an autosomal dominant amyloid cardiomyopathy. Homozygous patients are infrequently documented in case reports, and though there are larger studies among heterozygous patients, there is a lack of studies or reports comparing disease within a family.
In this case series, we discuss a 61-year-old African-American male who succumbed to heart failure secondary to cardiac amyloidosis while awaiting orthotopic heart transplantation. We compare his case with that of his sister, a 65-year-old African-American woman with a history of recurrent supraventricular tachycardia requiring radiofrequency ablation, and intermittent chest pain with chronically elevated troponin despite no evidence of coronary artery disease. The sister in question was found to be homozygous for the transthyretin (TTR) V122I mutation with evidence of infiltrative process on cardiac magnetic resonance imaging, while clinical testing verified a heterozygous genotype in the brother. Here, we compare the clinical course and imaging data for the aforementioned brother-sister pair in the context of the amyloidogenic transthyretin V122I gene variant.
Through this familial report, we aim to highlight the variations in expression both within this family and in comparison, to the population. We also hope to emphasize the importance of genetic testing of families at risk for this specific transthyretin variant within the African-American community especially as novel therapies begin to emerge.
约4%的非裔美国人在转甲状腺素蛋白中存在缬氨酸到异亮氨酸（V122I）的替换，这导致一种通常为四聚体的蛋白质倾向于解离成错误折叠的单体亚基。这些错误折叠的蛋白质随后会在病理上积累并导致常染色体显性遗传性淀粉样心肌病。纯合子患者在病例报告中很少有记录，尽管在杂合子患者中有更大规模的研究，但缺乏对一个家族内疾病进行比较的研究或报告。
在这个病例系列中，我们讨论了一名61岁的非裔美国男性，他在等待原位心脏移植时死于心脏淀粉样变性继发的心力衰竭。我们将他的病例与他的妹妹进行了比较，他的妹妹是一名65岁的非裔美国女性，有复发性室上性心动过速病史，需要进行射频消融，并且尽管没有冠状动脉疾病的证据，但肌钙蛋白长期升高伴有间歇性胸痛。经检测，这位妹妹是转甲状腺素蛋白（TTR）V122I突变的纯合子，心脏磁共振成像显示有浸润性病变，而临床检测证实其哥哥为杂合子基因型。在此，我们在淀粉样变性转甲状腺素蛋白V122I基因变异的背景下，比较了上述兄妹二人的临床病程和影像学数据。
通过这份家族报告，我们旨在强调这个家族内部以及与总体人群相比的表达差异。我们还希望强调对非裔美国社区中存在这种特定转甲状腺素蛋白变异风险的家族进行基因检测的重要性，特别是在新疗法开始出现的情况下。
