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NOTCH2NLC Intermediate-Length Repeat Expansions Are Associated with Parkinson Disease
Chang-He Shi1,2,3, Yu Fan1,4, Jing Yang1,2,3
1Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Intermediate-length NOTCH2NLC GGC repeat expansions were found in Parkinson disease (PD) patients, but not in controls. This suggests a potential link between these repeat expansions and PD development.
Area of Science:
- Neurogenetics
- Neurodegenerative Diseases
Background:
- Neuronal intranuclear inclusion disease (NIID) is associated with NOTCH2NLC GGC repeat expansions.
- The presence of these expansions in other neurodegenerative disorders is not well understood.
Purpose of the Study:
- To investigate the role of intermediate-length NOTCH2NLC GGC repeat expansions in Parkinson disease (PD).
Main Methods:
- Screening of 1,011 PD patients and 1,134 controls for GGC repeat expansions in NOTCH2NLC.
- Skin biopsy analysis for phospho-alpha-synuclein deposition.
- Fibroblast analysis from PD patients with repeat expansions.
Main Results:
- Eleven PD patients (1.1%) had intermediate-length NOTCH2NLC GGC repeat expansions (41-52 repeats).
- No repeat expansions were found in controls.
- Two patients with expansions showed phospho-alpha-synuclein deposition, confirming PD.
- Fibroblasts from these patients exhibited NOTCH2NLC upregulation and autophagic dysfunction.
Conclusions:
- Intermediate-length NOTCH2NLC GGC repeat expansions may be associated with Parkinson disease.
- Further research is needed to elucidate the precise role of these expansions in PD pathogenesis.
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