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이선민Sun Min Lee
아주대학교 의과대학
Alzheimers. Dement., Mar 2025, 21 (3) | https://doi.org/10.1002/alz.14566
Semantic variant primary progressive aphasia with ANXA11 p.D40G
Sun Min Lee 1, Soo Jin Yoon 2, Kyung Won Park 3, Ahro Kim 4, Hee Jin Kim 5, Na-Yeon Jung 6, Hyemin Jang 7, William W Seeley 8,9, Young-Eun Kim 10, So Young Moon 1, Eun-Joo Kim 11; Longitudinal study of Early onset dementia And Family members (LEAF) investigators
1Department of Neurology, Ajou University School of Medicine, Suwon, South Korea.
2Department of Neurology, Daejeon Eulji Medical Center, Eulji University, Daejeon, South Korea.
3Department of Neurology, Dong-A Medical Center, Dong-A University College of Medicine, Busan, South Korea.
4Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
5Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
6Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan, South Korea.
7Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
8Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
9Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
10Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, South Korea.
11Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
Young-Eun Kim, So Young Moon, and Eun-Joo Kim contributed equally.
Corresponding Authors: Young-Eun Kim, So Young Moon, Eun-Joo Kim
1Department of Neurology, Ajou University School of Medicine, Suwon, South Korea.
2Department of Neurology, Daejeon Eulji Medical Center, Eulji University, Daejeon, South Korea.
3Department of Neurology, Dong-A Medical Center, Dong-A University College of Medicine, Busan, South Korea.
4Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
5Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
6Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan, South Korea.
7Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
8Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
9Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
10Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, South Korea.
11Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
Young-Eun Kim, So Young Moon, and Eun-Joo Kim contributed equally.
Corresponding Authors: Young-Eun Kim, So Young Moon, Eun-Joo Kim
Abstract
Introduction: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD.
Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea.
Results: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS.
Discussion: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization.
Highlights: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C.
Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea.
Results: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS.
Discussion: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization.
Highlights: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-19)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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