The G41D mutation in SOD1-related amyotrophic lateral sclerosis exhibits phenotypic heterogeneity among individuals: A case report and literature review

RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. However, the misdiagnosis of ALS always occurs because of atypical clinical manifestations. Since mutations in Cu/Zn superoxide dismutase 1 (SOD1) have been implicated as causative and account for 20% of fALS cases, early genetic sequencing of suspected individuals in ALS pedigrees could be helpful. PATIENT CONCERNS: Here we report a Chinese family spanning three generations with fALS. A heterozygous c.125G>A (p.Gly42Asp) missense mutation in exon 2 of SOD1 gene was detected in our proband as well as her 2 siblings and next generation. Phenotypic diversity was also reported among symptomatic individuals. DIAGNOSES: Peripheral blood samples from the proband were collected and sent for polymerase chain reaction (PCR) and Sanger sequencing of the SOD1 gene at Sanvalley Diagnostics. The other 11 members in the studied family then underwent locus verification. INTERVENTIONS: Butylphthalide, Vitamin B12, Coenzyme Q10 and mouse nerve growth factor is given to the symptomatic members. OUTCOMES: The symptoms of our proband was not improved by treatments at a late stage. She passed away the fourth year of the disease due to respiratory failure. Two siblings of the proband were given active treatments once verified as carrier. Their symptoms are still limited to limb weakness. LESSONS: This study suggests genetic sequencing is a powerful tool for the diagnosis of familial ALS. Phenotypic heterogeneity exists among G41D-mutated individuals, which further highlights the importance of genomic strategies for early diagnosis.