Rösner Sabine, Pardo Luba M, Bertoli-Avella Aida M, Skrahina Volha, Engel Pierre, Schröder Sabine, Zielske Susan, Bonke Valerie, Kreth Janett, Westphal Gina, Reder Felix, Skobalj Snezana, Zielke Susanne, Bogdanovic Xenia, Grieger Paula, Rennecke Jörg, Skripuletz Thomas, Patten Monica, Aßmus Birgit, Hahn Katrin, Rolfs Arndt, Bauer Peter
CENTOGENE GmbH, 18055 Rostock, Germany.
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.
J Clin Med. 2024 Oct 17;13(20):6197. doi: 10.3390/jcm13206197.
: Hereditary transthyretin-related amyloidosis is a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the gene (hATTR amyloidosis). The current study describes the demographic, clinical, and genetic characteristics of patients with suspected hATTR amyloidosis. : This study is part of the "Hereditary transthyretin-related amyloidosis and longitudinal monitoring of -positive patients" (TRAMmoni) study. This study included 3167 participants, along with their clinical details. Principal component (PC) analysis was used to analyze their clinical symptomatology. Next-generation sequencing of the gene was performed and genotype-phenotype relationships were investigated. We compared the demographic and clinical characteristics using the principal components (PCs) and also compared participants with and without the pathogenic variants. We identified five main clinical phenotypes out of 22 single symptoms that explained 49% of the variation. The first two PCs referred to polyneuropathy and cardiomyopathy. We found significant differences between gender and PC-polyneuropathy and PC-cardiomyopathy, with male over-representation in the higher quantiles of PC-polyneuropathy and male under-representation in the lowest quantiles of PC-cardiomyopathy. We identified 92 participants with hATTR (3%), exhibiting 17 unique heterozygous variants. The p.Val50Met variant was the most frequent. Furthermore, 503 participants (20%) were identified with ATTR and no relevant variants (ATTRwt). We detected significant differences between the ATTRwt and hATTR groups, with male gender predominance in only the ATTRwt group and a positive family history of polyneuropathy and/or cardiomyopathy among the hATTR participants. : The current clinical and genetic characterization of this cohort serves as a foundation for further longitudinal monitoring and assessment.
遗传性转甲状腺素蛋白相关淀粉样变性是一种临床异质性常染色体显性疾病，由该基因的致病变异引起（hATTR淀粉样变性）。本研究描述了疑似hATTR淀粉样变性患者的人口统计学、临床和遗传特征。：本研究是“遗传性转甲状腺素蛋白相关淀粉样变性及阳性患者的纵向监测”（TRAMmoni）研究的一部分。本研究纳入了3167名参与者及其临床详细信息。使用主成分（PC）分析来分析他们的临床症状。对该基因进行了二代测序，并研究了基因型与表型的关系。我们使用主成分（PCs）比较了人口统计学和临床特征，还比较了有和没有该致病变异的参与者。我们在22种单一症状中确定了5种主要临床表型，这些表型解释了49%的变异。前两个主成分涉及多发性神经病和心肌病。我们发现性别与PC - 多发性神经病和PC - 心肌病之间存在显著差异，在PC - 多发性神经病较高分数段男性占比过高，而在PC - 心肌病最低分数段男性占比过低。我们确定了92名患有hATTR的参与者（3%），表现出17种独特的杂合变异。p.Val50Met变异最为常见。此外，503名参与者（20%）被确定为ATTR且无相关变异（ATTRwt）。我们在ATTRwt组和hATTR组之间检测到显著差异，仅ATTRwt组中男性占主导，而hATTR参与者中有多发性神经病和/或心肌病的阳性家族史。：该队列目前的临床和遗传特征为进一步的纵向监测和评估奠定了基础。
