Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
IDG/McGovern Institute for Brain Research at Tsinghua University, Beijing, China.
Medicine (Baltimore). 2022 Feb 11;101(6):e28771. doi: 10.1097/MD.0000000000028771.
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.
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.
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.
Butylphthalide, Vitamin B12, Coenzyme Q10 and mouse nerve growth factor is given to the symptomatic members.
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.
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.
肌萎缩侧索硬化症（ALS）是一种进行性和致命的神经退行性疾病。然而，由于不典型的临床表现，ALS 的误诊总是发生。由于铜/锌超氧化物歧化酶 1（SOD1）的突变被认为是致病原因，并占 fALS 病例的 20%，因此对 ALS 家系中疑似个体进行早期遗传测序可能会有所帮助。
在这里，我们报告了一个跨越三代的中国家族的 fALS。我们的先证者以及她的 2 个兄弟姐妹和下一代中发现 SOD1 基因外显子 2 中的杂合 c.125G>A（p.Gly42Asp）错义突变。有症状的个体也报告了表型多样性。
从先证者采集外周血样本，并送到 Sanvalley Diagnostics 进行聚合酶链反应（PCR）和 SOD1 基因的 Sanger 测序。研究家族中的其他 11 名成员随后进行了基因座验证。
给予有症状的成员丁苯酞、维生素 B12、辅酶 Q10 和鼠神经生长因子。
我们的先证者的症状在晚期治疗后没有改善。她因呼吸衰竭在疾病的第四年去世。先证者的 2 个兄弟姐妹在被确认为携带者后接受了积极治疗。他们的症状仍然仅限于四肢无力。
本研究表明，遗传测序是诊断家族性 ALS 的有力工具。G41D 突变个体存在表型异质性，这进一步强调了基因组策略对早期诊断的重要性。
