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.

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