{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:06:55Z","timestamp":1772168815859,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.138436.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["WT093205MA"],"award-info":[{"award-number":["WT093205MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["WT104033AIA"],"award-info":[{"award-number":["WT104033AIA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MR\/S01165X\/1, MR\/S005021\/1, G0601943"],"award-info":[{"award-number":["MR\/S01165X\/1, MR\/S005021\/1, G0601943"]}]},{"name":"Synaptopathies Strategic Award","award":["165908"],"award-info":[{"award-number":["165908"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the\n                    <ns3:italic>C9orf72<\/ns3:italic>\n                    gene being the most significant. However, the presence of\n                    <ns3:italic>C9orf72<\/ns3:italic>\n                    repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS. Methods We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the\n                    <ns3:italic>C9orf72<\/ns3:italic>\n                    gene, we performed Repeat-Primed PCR (RP-PCR). Results In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%).\n                    <ns3:italic>C9orf72<\/ns3:italic>\n                    repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. Conclusions Our results indicate that\n                    <ns3:italic>C9orf72<\/ns3:italic>\n                    hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.138436.2","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T09:05:05Z","timestamp":1709715905000},"page":"1113","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)"],"prefix":"10.12688","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5578-7213","authenticated-orcid":false,"given":"Mariam","family":"Kekenadze","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Rocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Turchetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Kvirkvelia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shorena","family":"Vashadze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eka","family":"Kvaratskhelia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maia","family":"Beridze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rauan","family":"Kaiyrzhanov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"1918-1929","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: a clinical review.","volume":"27","author":"P Masrori","year":"2020","journal-title":"Eur. 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We would like to respond to some of them.  1. Georgia is located in the Caucasus, neighboring countries are Armenia, Azerbaijan, Turkey, and Russia. After a thorough search of the literature using various languages, we were not able to find any relevant information about c9orf72 expansion prevalence in Armenia and Azerbaijan, however, there are some data available from Turkey and Russia, demonstrating low incidence in later countries, we depicted following in Eurasia map, Figure 3. Furthermore, there have not been any studies, including genetics, in the ALS population prior to this one in Georgia, indicating the significance of this research.  2. There is sparse information regarding the genetic architecture of the Georgian population, therefore it is difficult to conclude the homogeneity of the population. The study indeed represents the whole Georgian population, samples were gathered from different parts of Georgia, and results are published in different article:&nbsp;https:\/\/pubmed.ncbi.nlm.nih.gov\/37166887\/  3. We concluded that scientifically significant results would represent identifying a similar number of ALS patients in the Georgian population size according to worldwide incidence\/prevalence of the disease. Unfortunately, there is no data available regarding c9orf72 gene expansion prevalence in ALS patients in neighboring countries.  4. We agree with the reviewer.  5. C9orf72 positive cases in familial ALS in Belgium and Sweden, we used the following article: Smith BN, Newhouse S, Shatunov A, et al.: The C9ORF72 expansion mutation is a common cause of ALS+\/-FTD in Europe and has a single founder. Eur. J. Hum. Genet. 2013; 21(1): 102\u2013108, who reported these findings.&nbsp;  6. Thank you for pointing out the issue with privacy in Figshare, we will fix it.","URL":"https:\/\/f1000research.com\/articles\/12-1113\/v2#referee-comment-10569","order":1,"name":"referee-comment-10569","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.163149.r253260, Naoki Suzuki, Tohoku University Graduate School of Medicine, Sendai, 09 Mar 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/12-1113\/v2#referee-response-253260","order":2,"name":"referee-response-253260","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was funded in part, by Wellcome [WT093205MA, WT104033AIA, and the Synaptopathies Strategic Award, 165908]. This study was funded by the Medical research council (MRC) (MR\/S01165X\/1, MR\/S005021\/1, G0601943). Funding was used to cover the expenses of genetic testing. MK was supported by the EAN clinical fellowship award and Guarantors of Brain award to conduct the visit to the UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}