Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias

Bin Jiao; Lu Zhou; Yafang Zhou; Ling Weng; Xinxin Liao; Yun Tian; Lina Guo; Xixi Liu; Zhenhua Yuan; Xuewen Xiao; Yaling Jiang; Xin Wang; Qijie Yang; Chenping Li; Yuan Zhu; Lin Zhou; Weiwei Zhang; Junling Wang; Yu Li; Wenping Gu; Jie Yang; Jian Xia; Qing Huang; Jun Yin; Jin Xue; Ranhui Duan; Beisha Tang; Lu Shen

doi:10.1016/j.neurobiolaging.2020.01.010

Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias

Neurobiol Aging. 2020 May:89:142.e1-142.e7. doi: 10.1016/j.neurobiolaging.2020.01.010. Epub 2020 Jan 24.

Authors

Bin Jiao¹, Lu Zhou², Yafang Zhou³, Ling Weng¹, Xinxin Liao³, Yun Tian³, Lina Guo², Xixi Liu², Zhenhua Yuan², Xuewen Xiao², Yaling Jiang², Xin Wang², Qijie Yang², Chenping Li², Yuan Zhu², Lin Zhou³, Weiwei Zhang⁴, Junling Wang¹, Yu Li², Wenping Gu², Jie Yang², Jian Xia², Qing Huang², Jun Yin², Jin Xue⁵, Ranhui Duan⁵, Beisha Tang¹, Lu Shen⁶

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
³ National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
⁵ Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China. Electronic address: shenlu@csu.edu.cn.

PMID: 32081467
DOI: 10.1016/j.neurobiolaging.2020.01.010

Abstract

Recently, the (GGC)_n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy.

Keywords: Expanded repeats; NOTCH2NLC; Neurodegenerative dementia.

Publication types

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

MeSH terms

Aged
Alzheimer Disease / genetics*
China
Cohort Studies
DNA Repeat Expansion*
Female
Frontotemporal Dementia / genetics*
Genetic Association Studies
Humans
Intranuclear Inclusion Bodies / genetics
Leukoencephalopathies / genetics*
Male
Middle Aged
Neurodegenerative Diseases / genetics*
Receptor, Notch2 / genetics*

Substances

NOTCH2 protein, human
Receptor, Notch2

Supplementary concepts

Neuronal intranuclear inclusion disease