SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights.

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Tác giả: Masahiro Ando, Akihiro Hashiguchi, Yujiro Higuchi, Yu Hiramatsu, Takahiro Hobara, Fumikazu Kojima, Takeshi Matsushige, Jun Mitsui, Tomonori Nakamura, Satoshi Nozuma, Yuji Okamoto, Yusuke Sakiyama, Hiroshi Takashima, Shoji Tsuji, Chikashi Yano, Akiko Yoshimura, Jun-Hui Yuan

Ngôn ngữ: eng

Ký hiệu phân loại: 306.773 Sodomy

Thông tin xuất bản: Germany : Journal of neurology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 55064

BACKGROUND: Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of SOD1-related IPNs (SOD1-IPN) in a nationwide Japanese IPN cohort. METHODS: Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring SOD1 pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings. RESULTS: Seventeen patients with SOD1 pathogenic variants were identified, reinforcing SOD1's role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy. CONCLUSION: This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.
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