A Multicenter Study of Hereditary Transthyretin Amyloidosis in China.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-02-20 DOI:10.1002/ana.27203

Xujun Chu, Juan Kang, Jingwen Xu, Haishan Jiang, Zhi-Ying Wu, Qingping Wang, Wei Li, Jia Li, Xinghua Luan, Chong Sun, Zhangyu Zou, Min Zhu, Bin Chen, Xiaoxuan Liu, Meihong Zhou, Kang Du, Tao Huang, Dongsheng Fan, Zaiqiang Zhang, Daojun Hong, Jie Lin, Li Cao, Min Qian, Zhaoxia Wang, Yun Yuan, Yuwei Da, Hao Yu, Ruxu Zhang, Lingchao Meng

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引用次数: 0

Abstract

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.

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来源期刊

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.