Article Text
Abstract
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.
- phenotype
- dementia
- genotype
Data availability statement
Data are available upon reasonable request.
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Footnotes
CL and LD contributed equally.
Contributors CL and LD were responsible for the investigation, methodology and writing the original draft. JL was responsible for investigation and methodology. XH, DL, JW and SC contributed to the formal analysis. CM contributed to validation and methodology. LS and QX contributed to the formal analysis especially on genetic mutations. BP and LC contributed to funding acquisition and resources. JG was responsible for project administration, supervision, writing review and editing, funding acquisition and resources. All the authors are responsible for the overall content as the guarantor.
Funding This work was supported by National Key Research and Development Program of China (2020YFA0804500, 2020YFA0804501, 2016YFC1306300), National Natural Science Foundation of China (81550021, 30470618) and CAMS Innovation fund for Medical Sciences (2016-12M-1-004).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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