School of Biology, College of Science, University of Tehran, Tehran, Iran.
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Neurobiol Aging. 2019 Mar;75:225.e9-225.e14. doi: 10.1016/j.neurobiolaging.2018.11.003. Epub 2018 Nov 16.
Mutations in the same gene are sometimes the cause of different clinically diagnosed neurologic disorders; this emphasizes interrelationships between various neurologic diseases. In this light, we screened SLC52A3, which is the cause of Brown-Vialetto-Van Laere syndrome, and C19orf12, which is the cause of neurodegeneration with brain iron accumulation in 60 Iranian amyotrophic lateral sclerosis (ALS) patients without mutations in the 2 most important ALS-causing genes, SOD1 and C9orf72. To the best of our knowledge, neither SLC52A3 nor C19orf12 has been mutation-screened previously in ALS cohorts. Justification for screening SLC52A3 included notable clinical similarities between Brown-Vialetto-Van Laere syndrome and ALS, and justification for screening C19orf12 was known contribution of mitochondrial dysfunction to ALS etiology. Disease-causing variations in the 2 genes were not found among the ALS patients. TARDBP was screened in 107 patients, and a mutation (p.Gly348Cys) was identified in one. Detailed clinical data on the patient are presented. It appears that mutations in TARDBP in ALS patients of Iran are rare and occur at similar frequencies to European populations.
同一基因的突变有时是导致不同临床诊断的神经紊乱的原因；这强调了各种神经疾病之间的相互关系。有鉴于此，我们筛选了 SLC52A3（Brown-Vialetto-Van Laere 综合征的致病基因）和 C19orf12（伴有脑铁沉积的神经退行性变的致病基因），这两个基因在 60 名没有 SOD1 和 C9orf72 这两个最重要的 ALS 致病基因突变的伊朗肌萎缩侧索硬化症 (ALS)患者中筛选。据我们所知，此前在 ALS 患者群体中尚未对 SLC52A3 或 C19orf12 进行过突变筛查。筛选 SLC52A3 的理由包括 Brown-Vialetto-Van Laere 综合征和 ALS 之间存在显著的临床相似性，筛选 C19orf12 的理由是线粒体功能障碍已知对 ALS 的发病机制有影响。这两个基因中的致病变异在 ALS 患者中未被发现。我们对 107 名患者进行了 TARDBP 筛查，发现一名患者存在突变（p.Gly348Cys）。该患者的详细临床数据如下。伊朗的 ALS 患者中 TARDBP 突变罕见，其发生频率与欧洲人群相似。
