{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:36:06Z","timestamp":1760747766312,"version":"build-2065373602"},"reference-count":32,"publisher":"BMJ","issue":"6","funder":[{"name":"CAMS Innovation fund for Medical Sciences","award":["2016-12M-1-004"],"award-info":[{"award-number":["2016-12M-1-004"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81550021, 30470618"],"award-info":[{"award-number":["81550021, 30470618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0804500, 2020YFA0804501, 2016YFC1306300"],"award-info":[{"award-number":["2020YFA0804500, 2020YFA0804501, 2016YFC1306300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,12,22]]},"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The <jats:italic>GRN<\/jats:italic> mutations, especially of the loss of function type, are causative of frontotemporal dementia (FTD). However, several <jats:italic>GRN<\/jats:italic> variants can be found in other neurodegenerative diseases, such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease. So far, there have been over 300 <jats:italic>GRN<\/jats:italic> mutations reported globally. However, the genetic spectrum and phenotypic characteristics have not been fully elucidated in Chinese population.<\/jats:p>\n                  <jats:p>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 <jats:italic>GRN<\/jats:italic> were included in this study. Those with the pathogenic or likely pathogenic variants of other dementia-related genes were excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>14 subjects carried the rare variants of <jats:italic>GRN<\/jats:italic>. 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 <jats:italic>GRN<\/jats:italic> 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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The novel <jats:italic>GRN<\/jats:italic> variants identified in this study contribute to enrich the <jats:italic>GRN<\/jats:italic> mutation repertoire. There is phenotypic similarity and diversity among Chinese patients with the <jats:italic>GRN<\/jats:italic> mutations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109499","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T13:26:04Z","timestamp":1705411564000},"page":"543-548","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["<i>GRN<\/i> mutation spectrum and genotype\u2013phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-7456","authenticated-orcid":false,"given":"Caiyan","family":"Liu","sequence":"first","affiliation":[{"name":"Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liling","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenhui","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longze","family":"Sha","sequence":"additional","affiliation":[{"name":"Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[{"name":"Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liying","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Dongcheng-qu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"2025101713114986000_61.6.543.1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1471-4159.2007.04968.x","article-title":"Progranulin: normal function and role in neurodegeneration","volume":"104","author":"Eriksen","year":"2008","journal-title":"J Neurochem"},{"key":"2025101713114986000_61.6.543.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.015"},{"key":"2025101713114986000_61.6.543.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181bf997a"},{"key":"2025101713114986000_61.6.543.4","doi-asserted-by":"crossref","DOI":"10.1007\/s11910-016-0707-9","article-title":"Genetics of Frontotemporal dementia","volume":"16","author":"Olszewska","year":"2016","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2025101713114986000_61.6.543.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70194-7"},{"key":"2025101713114986000_61.6.543.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0009-8"},{"key":"2025101713114986000_61.6.543.7","doi-asserted-by":"crossref","unstructured":"Huang G , Jian J , Liu CJ . 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