Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China.
Amyloid. 2024 Dec;31(4):266-274. doi: 10.1080/13506129.2024.2383467. Epub 2024 Jul 31.
This study aims to delineate the clinical profiles of the hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) patients with A97S variant from southern China and the molecular characteristics of this mutant protein.
Fifteen ATTRv-PN patients with heterozygous A97S and one patient with homozygous A97S were included in the study. Serum TTR tetramer concentration was quantified through ultra-performance liquid chromatography. Stabilities of A97S-TTR were assessed through urea-mediated tryptophan fluorescence experiments, and nephelometry was employed in drug response assessment.
All patients were late-onset (≥50 years) with a mean age of onset at 59.26 ± 5.06 years old. Patients displayed a mixed phenotype featuring sensory-motor neuropathy with autonomic dysfunction and cardiac involvement, such as palpitations and chest pain. Electrophysiological studies showed generally axonal impairment of sensory and motor nerves. Tafamidis-treated patients showed significantly higher TTR tetramer concentrations, approaching healthy controls' levels. assessment showed that A97S-TTR was more kinetically stable than the V122I-TTR, and tetramer stabilisers inhibited A97S-TTR amyloid formation by more than 70%.
This study provides valuable insights into the clinical and molecular characteristics of ATTRv-PN patients with A97S from South China, particularly regarding the differences in disease progression and stability features.
本研究旨在描述中国南方遗传性转甲状腺素蛋白淀粉样多神经病（ATTRv-PN）患者 A97S 变异的临床特征及该突变蛋白的分子特征。
本研究纳入了 15 名杂合子 A97S 和 1 名纯合子 A97S 的 ATTRv-PN 患者。通过超高效液相色谱法定量血清 TTR 四聚体浓度。通过尿素介导的色氨酸荧光实验评估 A97S-TTR 的稳定性，并采用散射比浊法评估药物反应。
所有患者均为迟发性（≥50 岁），平均发病年龄为 59.26±5.06 岁。患者表现出混合表型，伴有感觉运动神经病和自主神经功能障碍以及心脏受累，如心悸和胸痛。电生理学研究显示，感觉和运动神经普遍存在轴索损伤。接受塔法米替治疗的患者 TTR 四聚体浓度显著升高，接近健康对照组水平。评估显示，A97S-TTR 的动力学稳定性优于 V122I-TTR，四聚体稳定剂使 A97S-TTR 淀粉样形成抑制率超过 70%。
本研究提供了中国南方 ATTRv-PN 患者 A97S 的临床和分子特征的有价值的见解，特别是关于疾病进展和稳定性特征的差异。
