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Genotype-phenotype correlations
Original research
GRN mutation spectrum and genotype–phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort
  1. Caiyan Liu1,
  2. Liling Dong2,
  3. Jie Wang2,
  4. Jie Li2,
  5. Xinying Huang2,
  6. Dan Lei2,
  7. Chenhui Mao2,
  8. Shanshan Chu2,
  9. Longze Sha3,
  10. Qi Xu3,
  11. Bin Peng2,
  12. Liying Cui2,
  13. Jing Gao2
  1. 1 Peking Union Medical College Hospital, Dongcheng-qu, China
  2. 2 Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China
  3. 3 Peking Union Medical College, Beijing, China
  1. Correspondence to Professor Jing Gao, Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China; gj107{at}163.com

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.

https://doi.org/10.1136/jmg-2023-109499

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    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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.