NOTCH2NLC-related disorders: the widening spectrum and genotype–phenotype correlation

GGC repeats in the NOTCH2NLC has been identified in patients with a group of neurodegenerative disorders. We review the NOTCH2NLC-related disorders and potential disease-causing mechanisms. We found that visual abnormalities may be NOTCH2NLC-specific, and the actual prevalence of the expansion in European patients may be potentially higher than reported. Repeat size and interruptions confer pleiotropic effects on clinical phenotype. The haploinsufficiency of the NOTCH2NLC may not be primarily involved in NOTCH2NLC-related disorders and a toxic gain-of-function mechanism possibly drives the pathogenesis. In summary, the NOTCH2NLC-related disorders are showing a widening spectrum and the genotype–phenotype correlation needs further investigation. (By Yu Fan, https://jmg.bmj.com/content/early/2021/10/20/jmedgenet-2021-107883 )

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