Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Neurobiol Aging. 2022 Apr;112:212-214. doi: 10.1016/j.neurobiolaging.2022.01.009. Epub 2022 Feb 4.
Recently, homozygous missense variants in ANXA1 were identified to cause parkinsonism by segregation analysis in a consanguineous family. However, no further replication has been conducted in a wider range of Parkinson's disease (PD) populations. To investigate the involvement of ANXA1 mutations in PD, we analyzed the rare variants in 743 Chinese early-onset PD (EOPD) patients (age at onset <50) using whole exome sequencing. The over-representation of rare variants in patients was examined with Fisher's exact test at allele and gene levels. We did not find the disease-causing variant described in the original study, and no patient carried other homozygous or compound heterozygous variants of ANXA1. Six rare missense mutations in ANXA1 were identified (minor allele frequency <0.01). No significant association was found between ANXA1 variants and PD at allele and gene levels. Genetic screening of ANXA1 mutations suggested rare variants of ANXA1 were rare in EOPD in the Asian ethnic background. Further explorations with larger sample size were warranted to better understand the role of ANXA1 in PD.
最近，通过对一个近亲家庭的分离分析，发现 ANXA1 中的纯合错义变异可导致帕金森病。然而，在更广泛的帕金森病 (PD) 人群中，没有进一步的复制。为了研究 ANXA1 突变是否与 PD 有关，我们使用全外显子组测序分析了 743 名中国早发性 PD (EOPD) 患者 (发病年龄 < 50 岁) 的罕见变异。使用 Fisher 精确检验在等位基因和基因水平上检查患者中罕见变异的过度表达。我们没有发现原始研究中描述的致病变异，也没有患者携带 ANXA1 的其他纯合或复合杂合变异。在 ANXA1 中发现了 6 个罕见的错义突变 (次要等位基因频率 < 0.01)。在等位基因和基因水平上，ANXA1 变异与 PD 之间均未发现显著相关性。ANXA1 突变的遗传筛查表明，在亚洲人群中，EOPD 中 ANXA1 的罕见变体很少。需要更大的样本量进一步探索，以更好地了解 ANXA1 在 PD 中的作用。
