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, 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","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> < 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, 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\",\"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> < 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}
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
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.