遗传性转甲状腺素蛋白淀粉样变性症-新加坡多民族东南亚队列的临床和遗传特征。
Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore.
机构信息
Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore.
Duke NUS Graduate Medical School, Singapore.
出版信息
J Neuromuscul Dis. 2021;8(4):723-733. doi: 10.3233/JND-210656.
BACKGROUND AND AIMS
Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort.
METHODS
Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed.
RESULTS
29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser).
CONCLUSION
Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.
背景和目的
在文献中，东南亚遗传性转甲状腺素蛋白淀粉样变性（ATTRv 淀粉样变性）的研究代表性不足。我们报告了一个多民族东南亚队列中这种疾病的独特表型和遗传特征。
方法
在新加坡国家神经科学研究所，我们在 13 年期间（2007-2020 年）确定了经基因证实的 ATTRv 淀粉样变性患者。回顾性回顾了临床、实验室、基因型和电生理特征。
结果
确定了 29 名 ATTRv 淀粉样变性患者，包括中国人、马来人、缅甸人、越南人和印度尼西亚人。躯体神经病是最常见的初始表现，其次是腕管综合征、自主神经功能障碍和心脏功能障碍。在 14 名患者中发现最常见的变体是 ATTR-A97S（p.Ala117Ser），占汉族患者的 66.7%和整个队列的 48.3%。5 名患者患有早发性疾病（年龄<50 岁），具有以下变体：ATTR-V30M（p.Val50Met）、ATTR-G47A（p.Gly67Ala）、ATTR-S50I（p.Ser70Ile）和 ATTR-A97S（p.Ala117Ser）；一名患者患有 ATTR-A97S（p.Ala117Ser），仅单侧腕管综合征，横腕韧带组织学检查发现淀粉样沉积物。所有早发性患者均有阳性家族史；两名患者分别患有 ATTR-S50I（p.Ser70Ile）和 ATTR-Ala97Ser（p.Ala117Ser），表现为母系遗传的预期。在 24 名晚发性疾病（年龄≥50 岁）患者中，两名患者有新的变体，ATTR-G66D（p.Glu86Asp）和 ATTR-A81V（p.Ala101Val），基于转甲状腺素蛋白淀粉样变性的组织学鉴定，证实这些变体是致病性的。其他鉴定的变体包括 ATTR-V30M（p.Val50Met）、ATTR-R34T（p.Arg54Thr）、ATTR-S50I（p.Ser70Ile）、ATTR-H88R（p.His108Arg）和 ATTR-A97S（p.Ala117Ser）。
结论
我们的研究进一步扩展了关于 ATTRv 淀粉样变性的基因型和表型知识。
Zotero 插件