GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.

Autor:	Liu C; Peking Union Medical College Hospital, Dongcheng-qu, China., Dong L; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Wang J; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Li J; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Huang X; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Lei D; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Mao C; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Chu S; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Sha L; Peking Union Medical College, Beijing, China., Xu Q; Peking Union Medical College, Beijing, China., Peng B; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Cui L; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China., Gao J; Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China gj107@163.com.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2024 May 21; Vol. 61 (6), pp. 543-548. Date of Electronic Publication: 2024 May 21.
DOI:	10.1136/jmg-2023-109499
Abstrakt:	Background: METHODS: The GRN mutations, especially of the loss of function type, are causative of frontotemporal dementia (FTD). However, several GRN variants can be found in other neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease. So far, there have been over 300 GRN mutations reported globally. However, the genetic spectrum and phenotypic characteristics have not been fully elucidated in Chinese population.The participants were from the dementia cohort of Peking Union Medical College Hospital (n=1945). They received history inquiry, cognitive evaluation, brain imaging and exome sequencing. The dementia subjects carrying the rare variants of the GRN were included in this study. Those with the pathogenic or likely pathogenic variants of other dementia-related genes were excluded. Results: 14 subjects carried the rare variants of GRN . They were clinically diagnosed with behavioural variant of FTD (n=2), non-fluent/agrammatic variant primary progressive aphasia (PPA, n=3), semantic variant PPA (n=1), AD (n=6) and mixed dementia (n=2). 13 rare variants of GRN were found, including 6 novel variants (W49X, S226G, M152I, A91E, G79E and A303S). The most prevalent symptom was amnesia (85.7%, 12/14), followed by psychiatric and behavioural disorder (78.6%, 11/14). In terms of lobar atrophy, temporal atrophy/hypometabolism was the most common (85.7%, 12/14), followed by parietal atrophy/hypometabolism (78.6%, 11/14). Conclusion: The novel GRN variants identified in this study contribute to enrich the GRN mutation repertoire. There is phenotypic similarity and diversity among Chinese patients with the GRN mutations. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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