Cappelli Francesco, Frusconi Sabrina, Bergesio Franco, Grifoni Elisa, Fabbri Alessia, Giuliani Costanza, Falconi Serena, Bonifacio Stefania, Perfetto Federico
aIntensive Cardiac Care Unit, Department of Heart and Vessels bRegional Amyloid Center Azienda Ospedaliera Universitaria Careggi cGenetic Diagnostics Unit, Laboratory Department, Careggi University Hospital dDepartment of Internal Medicine, University of Florence, Florence, Italy.
J Cardiovasc Med (Hagerstown). 2016 Feb;17(2):122-5. doi: 10.2459/JCM.0000000000000290.
Transthyterin amyloidosis is a life-threatening disorder caused by the deposition of hepatocyte-derived transthyretin (TTR) amyloid in various tissues and organs. The most common worldwide pathogenic variant with almost exclusive cardiac involvement is Val142Ile with an allele frequency of 3.5% in U.S. African-American population, but supposed extremely rare, with only sporadic cases in Caucasian patients. Unexpectedly, in our amyloidosis referral centre, we identified five patients (15.1% of all TTRm diagnosed patients, three families, two singleton) with Val142Ile variant belonging to unrelated families of Caucasian origin. Molecular study was performed in a total of 10 individuals of which three were Italian families (three affected individuals and five unaffected individuals) and two were singleton (one Italian patient and one patient from Argentine with Spanish ancestry). Sequence analysis of TTR gene revealed the presence of the heterozygous Val142Ile in the five affected patients and in five asymptomatic individuals. All probands underwent, at diagnosis, a complete clinical, echocardiographic and biohumoral evaluation. To the best of our knowledge, we describe the larger report of Caucasian patients with Val142Ile cardiomyopathy. All patients at diagnosis showed symptoms of heart failure with increased thickness of left ventricular walls and systo-diastolic left ventricular dysfunction. They also showed increased plasma values of NT-proBNP and troponin I. Our data confirm that Caucasian patients with the Val142Ile pathogenic variant have phenotypic manifestations similar to that of African-American one. Moreover, our data clearly show that Val142Ile pathogenic variant is not only an African-American mutation but could be also an underestimated Caucasian variant.
转甲状腺素蛋白淀粉样变性是一种由肝细胞衍生的转甲状腺素蛋白（TTR）淀粉样蛋白在各种组织和器官中沉积引起的危及生命的疾病。全球最常见的几乎仅累及心脏的致病变异是Val142Ile，在美国非裔人群中的等位基因频率为3.5%，但据推测极为罕见，在白种人患者中仅有散发病例。出乎意料的是，在我们的淀粉样变性转诊中心，我们发现了5例（占所有诊断为TTRm患者的15.1%，3个家族，2名单发患者）携带Val142Ile变异的白种人无关家族患者。对总共10名个体进行了分子研究，其中3个是意大利家族（3名患病个体和5名未患病个体），2名单发患者（1名意大利患者和1名有西班牙血统的阿根廷患者）。TTR基因序列分析显示，5名患病患者和5名无症状个体中存在杂合Val142Ile。所有先证者在诊断时均接受了全面的临床、超声心动图和生物体液评估。据我们所知，我们描述了关于Val142Ile心肌病白种人患者的最大规模报告。所有患者在诊断时均表现出心力衰竭症状，左心室壁厚度增加以及左心室收缩-舒张功能障碍。他们还表现出血浆NT-proBNP和肌钙蛋白I值升高。我们的数据证实，携带Val142Ile致病变异的白种人患者具有与非裔美国人相似的表型表现。此外，我们的数据清楚地表明，Val142Ile致病变异不仅是一种非裔美国人的突变，也可能是一种被低估的白种人变异。
