Long-read sequencing identified repeat expansions in the 5′UTR of the NOTCH2NLC gene from Chinese patients with neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) is a myth and has perplexed the neurologists for half a century, due to its high clinical heterogeneity with unknown genetic causes. This progressive neurodegenerative disease is characterized by the formation of eosinophilic hyaline intranuclear inclusions in neuronal system and multiple organs. In this article, the authors performed whole-genome sequencing (WGS) and long-read sequencing (LRS) on NIID patients identified with intranuclear inclusions by skin biopsy. The GGC repeated expansion in 5’UTR of the NOTCH2NLC gene were consistently found in both familial and sporadic cases, which were confirmed by repeat-primed PCR in fourteen adult-onset and one juvenile-onset patients. Together, the authors demonstrated GGC repeated expansion in 5’UTR of the NOTCH2NLC gene was associated with the pathogenesis of NIID. (By Dr. Jianwen Deng, https://jmg.bmj.com/content/early/2019/08/14/jmedgenet-2019-106268 )

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