PDF(Pubmed)
Abstract：
BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression.
METHODS: Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient\'s clinical presentation and family history.
CONCLUSIONS: Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.
METHODS: Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient\'s clinical presentation and family history.
CONCLUSIONS: Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.
摘要：
背景：遗传性转甲状腺素蛋白（ATTRv）淀粉样变性是一种罕见的，遗传异质性和表型可变的全身性疾病，其特征是错误折叠的甲状腺素运载蛋白原纤维在各种组织中沉积。ATTRv心肌病和进行性轴索多发性神经病是最常见的表现，导致严重残疾，并最终在大约十年内死亡。随着疾病修饰治疗方案的发展，及时诊断和开始治疗对于防止疾病快速进展至关重要.
方法：这里，我们报道了一名73岁的患者,该患者最初通过心内膜活检诊断为心脏野生型ATTR(ATTRwt)淀粉样变性.分子遗传分析揭示了一种新的TTR序列变体（p。Ala65Val），根据先前报道的TTR突变以及患者的临床表现和家族史，极有可能是淀粉样变性的。
结论：我们的发现扩大了已知致病性TTR突变的范围，并强调了对淀粉样变性患者进行彻底诊断检查的重要性，包括仔细的基因检测，以避免误诊和错过治疗机会，并能够进行级联检测和跟踪携带者。
方法：这里，我们报道了一名73岁的患者,该患者最初通过心内膜活检诊断为心脏野生型ATTR(ATTRwt)淀粉样变性.分子遗传分析揭示了一种新的TTR序列变体（p。Ala65Val），根据先前报道的TTR突变以及患者的临床表现和家族史，极有可能是淀粉样变性的。
结论：我们的发现扩大了已知致病性TTR突变的范围，并强调了对淀粉样变性患者进行彻底诊断检查的重要性，包括仔细的基因检测，以避免误诊和错过治疗机会，并能够进行级联检测和跟踪携带者。
