Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis

The unclear pathogenic mechanisms of neurodegenerative disorders stemming from NOTCH2NLC GGC repeat expansions drive focused research. Thus, a bibliometric and meta-analysis was conducted to uncover research trends and positivity rates in NOTCH2NLC. We conducted systematic searches in the Web of Science, PubMed, Embase, and Scopus databases for studies related to NOTCH2NLC up until August 2, 2023. Information regarding countries, institutions, authors, journals, and keywords of studies included in the Web of Science was analyzed and visualized. The positivity rates of NOTCH2NLC GGC repeat expansions across all screened patients and patients' families were pooled under the random-effects model. Publication bias and its impact were examined using funnel plots, Egger's linear regression, and trim-and-fill method. The bibliometric analysis, revealing pronounced publication growth, comprised 119 studies, which came from China and Japan particularly. "Neuronal intranuclear inclusion disease" emerged as a frequently used keyword. The meta-analysis comprised 36 studies, indicating global positivity rates of 1.79% (95% CI, 0.75-3.17) for all patients and 2.00% (95% CI, 0.26-4.78) for patients' families. Subgroup analyses based on region and phenotype suggested the highest NOTCH2NLC positivity rates in Taiwan population (5.42%, 95% CI 0.08-16.89) and in leukoencephalopathy-dominant patients (8.25%, 95% CI, 3.01-15.60). Sensitivity analysis affirmed the robustness of results. In conclusion, NOTCH2NLC GGC repeat expansions exhibit rare globally, primarily in East Asia, and leukoencephalopathy-dominant patients, emphasizing regional and phenotypic distinctions. Emerging focal points in NOTCH2NLC researches underscore the need for collaborative exploration.