Unusual electrophysiological findings in a Chinese ALS 4 family with SETX-L389S mutation: a three-year follow-up
- PDF / 1,040,516 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 20 Downloads / 140 Views
ORIGINAL COMMUNICATION
Unusual electrophysiological findings in a Chinese ALS 4 family with SETX‑L389S mutation: a three‑year follow‑up Lin Lei1 · Hai Chen1 · Yan Lu1 · Wenjia Zhu1 · Yasheng Ouyang1 · Jianying Duo1 · Zhiguo Chen2,3,4 · Yuwei Da1 Received: 22 August 2020 / Revised: 23 September 2020 / Accepted: 25 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Amyotrophic lateral sclerosis type 4 (ALS4) is a familial form of ALS caused by mutations in the SETX gene. To date, there are seven unrelated ALS4 families with four missense mutations (L389S, T31I, R2136H, and M386T) in SETX. ALS4 is characterized by early onset, distal muscle weakness and atrophy, pyramidal signs, and the absence of sensory deficits. Motor conduction studies often present normality or reduced amplitudes of compound muscle action potential (CMAP). The conduction blocks (CBs) are rare and only observed in one male of an Italian ALS4 family. Our study showed that seven symptomatic patients presented the classical ALS4 phenotype with two asymptomatic females in a Chinese family spanning three generations. Sequencing analysis revealed a heterozygous c.1166T > C/p.L389S mutation in SETX that co-segregated with disease phenotype in the family. The same mutation has been identified previously in three ALS4 families from the United States and Italy, respectively. Specifically, three young males presented multiple CBs and abnormal temporal dispersions (TD) in the median, ulnar and tibial nerves over the three-year follow-up period. Moreover, for the first time, we found that senataxin was also expressed in the myelin sheath of peripheral nerves besides axons. The study indicates that CBs and abnormal TD are the characteristics in the ALS4 family, providing pivotal familial evidence of CBs and TD of motor nerves in ALS4. The unusual electrophysiological features may be associated with the expression of senataxin in peripheral nerves. Keywords Amyotrophic · Lateral sclerosis (ALS) · Familial · SETX · Conduction block · Temporal dispersion · Electrophysiology
Introduction Lin Lei, Hai Chen and Yan Lu have contributed equally to this manuscript. * Zhiguo Chen [email protected] * Yuwei Da [email protected] 1
Department of NEUROLOGY, Xuanwu Hospital, Capital Medical University, Changchun Street, Beijing 100053, China
2
Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Cell Therapy Center, National Clinical Research Center for Geriatric Diseases, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China
3
Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
4
Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease affecting upper and lower motor neurons, leading to progressive muscle weakness and atrophy. Nearly 10% of ALS patients are familial ALS (fALS) [1]. ALS4 is a rare form of autosom
Data Loading...
