目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及...目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及中国知网、万方数据库中关于Ser77Tyr突变所致ATTR-PN患者以及Pubmed、Web of Science数据库中关于Val30Met突变所致ATTR-PN患者的文献,提取患者的临床特征,汇总后比较Ser77Tyr、Val30Met突变所致ATTR-PN患者临床特征的差异。结果(1)收治患者的转甲状腺素蛋白(TTR)基因Sanger测序结果显示Ser77Tyr杂合致病性突变,刚果红染色患者发病2.5年时的胃窦活检标本显示淀粉样物质沉积。(2)最终汇总78例Ser77Tyr突变所致ATTR-PN患者,其多于50~60岁发病;男性发病率高(74.4%);多有阳性家族史(78.0%);首发症状以感觉障碍症状最常见(72.0%),数年内发展到周围神经广泛受累,同时合并普遍的心脏损害(96.4%);神经电生理检查示以轴索损害和腕管综合征表现为主;组织活检阳性率高(84.8%)。(3)汇总早发型、晚发型Val30Met突变所致ATTR-PN患者192例、96例。Ser77Tyr突变所致ATTR-PN患者深感觉障碍发生率(58.5%)高于早发型Val30Met突变所致ATTR-PN患者(28.6%),差异有统计学意义(P<0.05)。与晚发型Val30Met突变所致ATTR-PN患者比较,Ser77Tyr突变所致ATTR-PN患者浅感觉障碍发生率增高(56.3%vs.75.0%),肢体无力发生率降低(65.6%vs.48.3%),差异均有统计学意义(P<0.05)。Ser77Tyr突变所致ATTR-PN患者腕管综合征发生率(75.4%)高于早发型、晚发型Val30Met突变所致ATTR-PN患者(10.8%、25.0%),心脏损害发生率(96.4%)高于早发型Val30Met突变所致ATTR-PN患者(80.5%),差异均有统计学意义(P<0.05)。结论Ser77Tyr突变所致ATTR-PN患者具有一些相对独特的临床特征:大小纤维损害相对均衡、腕管综合征突出、心脏病变明显等,及早识别这些特征并完善活检和基因检测,有助于早期诊断。展开更多
Objective To study the clinical and genetic features of familiar amyloid polyneuropathy (FAP). Methods Three families of suspected FAP in China mainland and Macao were investigated on aspects of clinical manifestation...Objective To study the clinical and genetic features of familiar amyloid polyneuropathy (FAP). Methods Three families of suspected FAP in China mainland and Macao were investigated on aspects of clinical manifestations, histological features, and gene analysis. Results All the 3 families had the clinical features of sensory and motor polyneuropathies, and notable vegetative nerve involvements. Affected cases of one family had ultrasound proved cardiomyopathy. Histological studies showed amyloid deposition in all the biopsy tissues of the affected cases of the 3 families, and anti-transthyretin antisera staining was positive in 3 cases of one family. Gene analysis confirmed that mutation types were amyloidogenic transthyretin (ATTR) Val30Met, Phe33Val, and Gly67Glu in the 3 families respectively. The ATTR Gly67Glu family had a shorter survival time due to the heart involvement compared with the other 2 families. Conclusion FAP is an autosomal dominant inherited disease, with its clinical manifestations related to the type of genetic mutation.展开更多
文摘目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及中国知网、万方数据库中关于Ser77Tyr突变所致ATTR-PN患者以及Pubmed、Web of Science数据库中关于Val30Met突变所致ATTR-PN患者的文献,提取患者的临床特征,汇总后比较Ser77Tyr、Val30Met突变所致ATTR-PN患者临床特征的差异。结果(1)收治患者的转甲状腺素蛋白(TTR)基因Sanger测序结果显示Ser77Tyr杂合致病性突变,刚果红染色患者发病2.5年时的胃窦活检标本显示淀粉样物质沉积。(2)最终汇总78例Ser77Tyr突变所致ATTR-PN患者,其多于50~60岁发病;男性发病率高(74.4%);多有阳性家族史(78.0%);首发症状以感觉障碍症状最常见(72.0%),数年内发展到周围神经广泛受累,同时合并普遍的心脏损害(96.4%);神经电生理检查示以轴索损害和腕管综合征表现为主;组织活检阳性率高(84.8%)。(3)汇总早发型、晚发型Val30Met突变所致ATTR-PN患者192例、96例。Ser77Tyr突变所致ATTR-PN患者深感觉障碍发生率(58.5%)高于早发型Val30Met突变所致ATTR-PN患者(28.6%),差异有统计学意义(P<0.05)。与晚发型Val30Met突变所致ATTR-PN患者比较,Ser77Tyr突变所致ATTR-PN患者浅感觉障碍发生率增高(56.3%vs.75.0%),肢体无力发生率降低(65.6%vs.48.3%),差异均有统计学意义(P<0.05)。Ser77Tyr突变所致ATTR-PN患者腕管综合征发生率(75.4%)高于早发型、晚发型Val30Met突变所致ATTR-PN患者(10.8%、25.0%),心脏损害发生率(96.4%)高于早发型Val30Met突变所致ATTR-PN患者(80.5%),差异均有统计学意义(P<0.05)。结论Ser77Tyr突变所致ATTR-PN患者具有一些相对独特的临床特征:大小纤维损害相对均衡、腕管综合征突出、心脏病变明显等,及早识别这些特征并完善活检和基因检测,有助于早期诊断。
文摘Objective To study the clinical and genetic features of familiar amyloid polyneuropathy (FAP). Methods Three families of suspected FAP in China mainland and Macao were investigated on aspects of clinical manifestations, histological features, and gene analysis. Results All the 3 families had the clinical features of sensory and motor polyneuropathies, and notable vegetative nerve involvements. Affected cases of one family had ultrasound proved cardiomyopathy. Histological studies showed amyloid deposition in all the biopsy tissues of the affected cases of the 3 families, and anti-transthyretin antisera staining was positive in 3 cases of one family. Gene analysis confirmed that mutation types were amyloidogenic transthyretin (ATTR) Val30Met, Phe33Val, and Gly67Glu in the 3 families respectively. The ATTR Gly67Glu family had a shorter survival time due to the heart involvement compared with the other 2 families. Conclusion FAP is an autosomal dominant inherited disease, with its clinical manifestations related to the type of genetic mutation.
