Department of Neurology, Peking University Third Hospital, Beijing, People R China.
Department of Neurology, Peking University Third Hospital, Beijing, People R China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, People R China.
Neurobiol Aging. 2019 Feb;74:235.e9-235.e12. doi: 10.1016/j.neurobiolaging.2018.09.020. Epub 2018 Sep 22.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. A recent study has identified mutations in the ANXA11 gene (encoding the calcium-binding protein annexin A11) associated with ALS. Mutation screening of ANXA11 protein-coding exons was performed in a Chinese cohort of 434 patients with sporadic ALS and 50 index patients with familial ALS. Polymerase chain reaction and Sanger sequencing were used for mutation detection. We failed to discover an N-terminal mutation, which was common in the Caucasian cohort. We revealed two rare heterozygous missense variants, c.878C>T (p.A293V) and c.921C>G (p.I307M), which are absent from the population databases and non-neurological controls. They are both located in the conserved annexin domain. The carriers of the mutation exhibited the classical ALS phenotype without cognitive impairment. Our results suggested that further functional studies for these variants are required to support the pathogenicity.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病。最近的一项研究已经确定了与 ALS 相关的 ANXA11 基因突变（编码钙结合蛋白膜联蛋白 A11）。在一个由 434 名散发性 ALS 患者和 50 名家族性 ALS 索引患者组成的中国队列中，对 ANXA11 蛋白编码外显子进行了突变筛选。使用聚合酶链反应和 Sanger 测序进行突变检测。我们未能发现常见于白种人群的 N 端突变。我们揭示了两种罕见的杂合错义变异，c.878C>T（p.A293V）和 c.921C>G（p.I307M），它们不存在于人群数据库和非神经对照中。它们都位于保守的膜联蛋白结构域中。携带该突变的患者表现出经典的 ALS 表型，没有认知障碍。我们的结果表明，需要进一步进行这些变异的功能研究，以支持其致病性。
