CYLD variants identified in Alzheimer's disease and frontotemporal dementia patients

Xuewen Xiao; Tianyan Xu; Hui Liu; Xixi Liu; Xinxin Liao; Yafang Zhou; Lu Zhou; Xin Wang; Yuan Zhu; Qijie Yang; Xiaoli Hao; Yingzi Liu; Hong Jiang; Jifeng Guo; Junling Wang; Beisha Tang; Jinchen Li; Lu Shen; Bin Jiao

doi:10.1002/acn3.51655

CYLD variants identified in Alzheimer's disease and frontotemporal dementia patients

Ann Clin Transl Neurol. 2022 Oct;9(10):1596-1601. doi: 10.1002/acn3.51655. Epub 2022 Aug 24.

Authors

Xuewen Xiao¹, Tianyan Xu¹, Hui Liu¹, Xixi Liu¹, Xinxin Liao^{2

3

4

5

6}, Yafang Zhou^{2

3

4

6}, Lu Zhou¹, Xin Wang¹, Yuan Zhu¹, Qijie Yang¹, Xiaoli Hao¹, Yingzi Liu¹, Hong Jiang^{1

2

3

4

5}, Jifeng Guo^{1

2

3

4

5}, Junling Wang^{1

2

3

4

5}, Beisha Tang^{1

2

3

4

5}, Jinchen Li^{2

3

4

5}, Lu Shen^{1

2

3

4

5

7}, Bin Jiao^{1

2

3

4

5}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
² Bioinformatics Center and National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China.
³ Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China.
⁴ Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
⁵ Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
⁶ Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
⁷ Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.

Abstract

Objectives: CYLD was a novel causative gene for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis. Given the clinical and pathological overlap of FTD and Alzheimer's disease (AD), it is necessary to screen CYLD in AD patients and FTD patients in the Chinese population.

Methods: In our study, using a targeted sequencing panel, we sequenced the CYLD gene in a large cohort of 2485 participants in the Chinese population, including 1008 AD patients, 105 FTD patients, and 1372 controls.

Results: In the present study, the average onset age of AD and FTD patients was 66.84 ± 30.42 years old and 60 ± 10.00 years old, respectively. Our study reported three novel CYLD variants: p.Phe288Leu (patient No. 1, AD), p.Tyr485Phe (patients No. 6-9, all AD) and p.Thr951Ala (patient No. 10, AD), plus a previously reported variant: p.Arg397Ser (patient No. 2-5, AD and No. 11, FTD). These variants were absent in our in-house controls and predicted to be deleterious according to the MutationTaster. The variant carriers were composed of 10 AD patients and one FTD patient, and the average onset age was 61.2 ± 10.9 years. The frequency of CYLD variants in AD was similar to that in FTD, which was 0.99% (10/1008) and 0.95% (1/105), respectively.

Interpretation: Our finding extended the genotype and phenotype of the CYLD gene and demonstrated that CYLD rare damaging variants may be implicated in AD and FTD pathogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / genetics
Amyotrophic Lateral Sclerosis* / genetics
Deubiquitinating Enzyme CYLD* / genetics
Frontotemporal Dementia* / genetics
Genotype
Humans

Substances

CYLD protein, human
Deubiquitinating Enzyme CYLD

Grants and funding

This work was funded by Hunan Innovative Province Construction Project grant 2019SK2335; Hu‐Xiang Youth Project grant 2021RC3028; National Major Projects in Brain Science and Brain‐like Research grant 2021ZD0201803; the National Key R&D Program of China grant 2020YFC2008500; the National Natural Science Foundation of China grants 81971029, 82071216, and 81901171; Youth Program of Science Foundation of Xiangya Hospital grants 2018Q017 and 2018Q020.