Objective: We aimed to investigate whether NOTCH2NLCGGC repeats have a role in dystonia.

Background: Expanded GGC repeatin the 5′ untranslated region of the NOTCH2NLCgene has been identified to be the cause of neuronal inclusion disease. Later, expanded NOTCH2NLCGGC repeatswere detected also in a range of neurological diseases including essential tremor, Parkinson disease, inherited neuropathies, and oculopharyngodistal myopathy.

Method: The NOTCH2NLCGGC expansions repeatswere screened using polymerase chain reaction tests in dystonia patientsand healthy controls (HCs). The frequency of the expanded GGC repeats in dystonia was compared withHCs.

Results: A total of 270 patients with dystonia and 32 healthy controls were recruited. All the patients have undergone whole exome sequencing to exclude known causative genes for dystonia. Three patients with dystonia were identified as carrying NOTCH2NLCGGCrepeatexpansions of more than 40 units. None of the HCs carried the expansions of more than 40 units. One patient presented with cervical dystonia, head tremor, dysarthria, and ataxia had a repeat GGC expansions of 107 units.The brain magnetic resonance imaging (MRI) showed demyelination in white matter.One patient presented with cervical dystonia, hand tremor, and parkinsonism had a repeat GGC expansions of 94 units. The brain MRI showed leukoencephalopathy. One patient who presented withisolated cervicaldystonia carried a GGCrepeats of 50 units. His brain MRI was normal, and his unaffected parents had normal GGC repeats (16 and 17 units, respectively).

Conclusion: Our study suggested a role of expanded NOTCH2NLCGGC repeats in dystonia, paving way for future research.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-notch2nlc-repeat-expansions-with-dystonia/