中国遗传性甲状腺转蛋白淀粉样变的多中心研究。

IF 7.7 1区 医学 Q1 CLINICAL NEUROLOGY
Xujun Chu MD, Juan Kang MD, Jingwen Xu MD, Haishan Jiang MD, Zhi-Ying Wu MD, Qingping Wang MD, Wei Li MD, Jia Li MD, Xinghua Luan MD, Chong Sun MD, Zhangyu Zou MD, Min Zhu MD, Bin Chen MD, Xiaoxuan Liu MD, Meihong Zhou MD, Kang Du MD, Tao Huang PhD, Dongsheng Fan MD, Zaiqiang Zhang MD, Daojun Hong MD, Jie Lin MD, Li Cao MD, Min Qian MD, Zhaoxia Wang MD, Yun Yuan MD, Yuwei Da MD, Hao Yu MD, Ruxu Zhang MD, Lingchao Meng MD
{"title":"中国遗传性甲状腺转蛋白淀粉样变的多中心研究。","authors":"Xujun Chu MD,&nbsp;Juan Kang MD,&nbsp;Jingwen Xu MD,&nbsp;Haishan Jiang MD,&nbsp;Zhi-Ying Wu MD,&nbsp;Qingping Wang MD,&nbsp;Wei Li MD,&nbsp;Jia Li MD,&nbsp;Xinghua Luan MD,&nbsp;Chong Sun MD,&nbsp;Zhangyu Zou MD,&nbsp;Min Zhu MD,&nbsp;Bin Chen MD,&nbsp;Xiaoxuan Liu MD,&nbsp;Meihong Zhou MD,&nbsp;Kang Du MD,&nbsp;Tao Huang PhD,&nbsp;Dongsheng Fan MD,&nbsp;Zaiqiang Zhang MD,&nbsp;Daojun Hong MD,&nbsp;Jie Lin MD,&nbsp;Li Cao MD,&nbsp;Min Qian MD,&nbsp;Zhaoxia Wang MD,&nbsp;Yun Yuan MD,&nbsp;Yuwei Da MD,&nbsp;Hao Yu MD,&nbsp;Ruxu Zhang MD,&nbsp;Lingchao Meng MD","doi":"10.1002/ana.27203","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (<i>p</i> &lt; 0.001).</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025;97:1158–1167</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1158-1167"},"PeriodicalIF":7.7000,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Multicenter Study of Hereditary Transthyretin Amyloidosis in China\",\"authors\":\"Xujun Chu MD,&nbsp;Juan Kang MD,&nbsp;Jingwen Xu MD,&nbsp;Haishan Jiang MD,&nbsp;Zhi-Ying Wu MD,&nbsp;Qingping Wang MD,&nbsp;Wei Li MD,&nbsp;Jia Li MD,&nbsp;Xinghua Luan MD,&nbsp;Chong Sun MD,&nbsp;Zhangyu Zou MD,&nbsp;Min Zhu MD,&nbsp;Bin Chen MD,&nbsp;Xiaoxuan Liu MD,&nbsp;Meihong Zhou MD,&nbsp;Kang Du MD,&nbsp;Tao Huang PhD,&nbsp;Dongsheng Fan MD,&nbsp;Zaiqiang Zhang MD,&nbsp;Daojun Hong MD,&nbsp;Jie Lin MD,&nbsp;Li Cao MD,&nbsp;Min Qian MD,&nbsp;Zhaoxia Wang MD,&nbsp;Yun Yuan MD,&nbsp;Yuwei Da MD,&nbsp;Hao Yu MD,&nbsp;Ruxu Zhang MD,&nbsp;Lingchao Meng MD\",\"doi\":\"10.1002/ana.27203\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (<i>p</i> &lt; 0.001).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025;97:1158–1167</p>\\n </section>\\n </div>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\"97 6\",\"pages\":\"1158-1167\"},\"PeriodicalIF\":7.7000,\"publicationDate\":\"2025-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ana.27203\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.27203","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:遗传性甲状腺转蛋白淀粉样变性(ATTRv)是一种常染色体显性遗传病,其特征是甲状腺转蛋白(TTR)蛋白的错误折叠和沉积。本研究旨在描述中国大型多中心队列中ATTRv的临床和遗传特征。方法:来自14个中心的患者纳入研究。总结所有患者的临床及遗传特点。对不同性别子代外周血白细胞线粒体DNA (mtDNA)进行检测。结果:共鉴定出来自148个家庭的attv患者202例。平均发病年龄50.6±12.4岁。其中迟发性(≥50岁)117例(57.9%),早发性85例(42.1%)。总体而言,长度依赖性轴索感觉运动周围神经病变是主要表型(89.1%)。共鉴定出42个杂合错义变异和1个缺失变异。最常见的变异是Val30Met(19.8%)和Ala97Ser(15.8%),在我们的队列中,Val30Met和Ala97Ser的患者大多是晚发性的。死亡39例,平均年龄56.1±13.5岁。不同性别对后代-父母对的期望不同,母子对的期望最大。母亲后代的mtDNA拷贝数超过父亲后代的mtDNA拷贝数(p)解释:本研究强调,中国的ATTRv患者在其初始症状上表现出高度的异质性。在这个队列中观察到的最常见的变异是Val30Met。mtDNA拷贝数显示出与性别相关的影响。这些结果可以影响ATTRv的诊断和患者护理策略。Ann neurol 2025。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Multicenter Study of Hereditary Transthyretin Amyloidosis in China

Objective

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.

Methods

Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.

Results

A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (p < 0.001).

Interpretation

This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025;97:1158–1167

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Annals of Neurology
Annals of Neurology 医学-临床神经学
CiteScore
18.00
自引率
1.80%
发文量
270
审稿时长
3-8 weeks
期刊介绍: Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信