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This cross-sectional observational study aimed to characterise the clinical features of<jats:italic>NOTCH2NLC<\/jats:italic>-related NIID in China.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with<jats:italic>NOTCH2NLC<\/jats:italic>-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the 247 patients with<jats:italic>NOTCH2NLC<\/jats:italic>-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=\u22120.196, p&lt;0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p&lt;0.05). In NIID pedigrees, significant genetic anticipation was observed (p&lt;0.05) without repeat instability (p=0.454) during transmission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of<jats:italic>NOTCH2NLC<\/jats:italic>-related NIID.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2022-329772","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T17:50:25Z","timestamp":1663955425000},"page":"1289-1298","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["Clinical features of<i>NOTCH2NLC<\/i>-related neuronal intranuclear inclusion 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