Meng Yaping, Li Wenping, Zhang Yanxin, Li Yaoru, He Yong, Zhang Nan
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China.
Eur J Neurol. 2025 May;32(5):e70187. doi: 10.1111/ene.70187.
Semantic variant primary progressive aphasia (svPPA) is typically a sporadic disorder, and few cases have been linked to ANXA11 mutations. Comprehensive analyses of genetic mutations in svPPA are limited. Furthermore, the clinical and genetic distinctions between typical svPPA and right temporal variant frontotemporal dementia (rtvFTD) are poorly understood.
A 68-year-old patient with svPPA carrying a heterozygous ANXA11 c.119A>G (p.D40G) mutation underwent comprehensive neuropsychological, neuroimaging, and genetic assessments at baseline and at the one-year follow-up timepoint. Additionally, systematic reviews were conducted to identify reported cases of ANXA11 mutations in the FTD spectrum and the genetic mutations associated with svPPA. Clinical-genetic profiles of typical svPPA and rtvFTD were compared based on data from the literature.
Thirty-two patients with ANXA11 mutations were identified, including 11 with pure FTD phenotypes and the majority exhibiting FTD-amyotrophic lateral sclerosis (ALS). Among 167 svPPA-related cases, MAPT, GRN, and C9ORF72 mutations were most frequently implicated; ANXA11 mutations were primarily identified in East Asian patients. Comparative analysis revealed overlapping age at onset, disease duration, sex distribution, and APOE ε4 allele frequencies between typical svPPA and rtvFTD but differing clinical presentations.
This study reports a case of typical svPPA in China associated with the ANXA11 p.D40G mutation without ALS-related features. Our findings highlight the importance of ANXA11 mutations in FTD pathogenesis.
语义变异型原发性进行性失语（svPPA）通常是一种散发性疾病，仅有少数病例与膜联蛋白A11（ANXA11）突变有关。对svPPA基因突变的全面分析有限。此外，典型svPPA与右颞叶变异型额颞叶痴呆（rtvFTD）之间的临床和基因差异尚不清楚。
一名68岁携带杂合ANXA11基因c.119A>G（p.D40G）突变的svPPA患者在基线及一年随访时间点接受了全面的神经心理学、神经影像学和基因评估。此外，还进行了系统综述，以确定FTD谱系中报道的ANXA11突变病例以及与svPPA相关的基因突变。基于文献数据比较了典型svPPA和rtvFTD的临床-基因特征。
共鉴定出32例ANXA11突变患者，其中11例为纯FTD表型，大多数表现为FTD-肌萎缩侧索硬化（ALS）。在167例与svPPA相关的病例中，微管相关蛋白tau（MAPT）、原肌球蛋白9（GRN）和9号染色体开放阅读框72（C9ORF72）突变最为常见；ANXA11突变主要在东亚患者中发现。比较分析显示，典型svPPA和rtvFTD在发病年龄、病程、性别分布和载脂蛋白Eε4等位基因频率方面存在重叠，但临床表现不同。
本研究报告了1例中国典型svPPA病例，该病例与ANXA11 p.D40G突变相关，无ALS相关特征。我们的研究结果强调了ANXA11突变在FTD发病机制中的重要性。
