Characteristics of SOD1 gene mutation in patients with amyotrophic lateral sclerosis and its relationship with clinical phenotype

Ruipeng Wu^1,#, Chunhui Liu^2,#, Cheng Gu¹, Xiaojuan Hu¹, Bin Feng¹, Bingyan Chai³, Yi Zhang^1,*

¹Department of Neurology, GanSu Provincial Hospital, Lanzhou, PR China - ²Department of Andrology, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, PR China - ³Gansu University of Chinese Medicine, Lanzhou, PR China

Objective: To analyse the type of copper-zinc superoxide dismutase (SOD1) gene mutation and its relationship with clinical phenotype in patients with amyotrophic lateral sclerosis (ALS). 

Methods: Twenty-seven patients with ALS (probands of familial ALS) diagnosed and treated in the Department of Neurology of our hospital from 2015 to 2019 were selected for this study. The clinical data and peripheral blood samples of all patients were collected, and five exons of the SOD1 gene on 27 probands were detected via the real-time quantitative PCR method and direct sequencing method to analyse their relationships with the clinical phenotype.

Results: The PCR method was used to detect five exons of the SOD1 gene in 38 patients. The results showed that three heterozygous missense mutations were detected in 6 probands, and the detection rate of SOD1 positive mutations was 22.22%. There were 13 patients with the p.His46Arg (C:140A >G) mutation in their families, and all of them had unilateral distal lower extremity onset in which the lower motor neuron lesion was dominant, the F1-III8 reflex was active, the survival time of the F1 and XX probands were 18 and 20 years, respectively, and the survival time of patients in the F2 and F3 families reached 20 years. Three cases in the F4 family had lower extremity onset, with F4-III5 producing lower extremity proximal onset and upper and lower motor neuron damage. The F5-II8 cases in the F5 family showed lower motor neuron damage, and the survival time of patients was 3 to 4 years. The F6-III1 case showed weakness at  the distal end of the unilateral upper limb, but the symptoms were mild and accompanied by mild atrophy of the small muscles of the hand and tingling pain in the hand. An Electromyogram (EMG) indicated extensive neurogenic damage and slow progression of the disease.

Conclusion: SOD1 gene mutations still dominate in familial ALS patients, with most SOD1 mutations being associated with clinical phenotypes, and p.His46Arg (C:140A>G) mutations having characteristic clinical phenotypes.