{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:30:14Z","timestamp":1787740214147,"version":"build-2784847793"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Gly83Arg variation is a type of <jats:italic>TTR<\/jats:italic> mutation specific to the Chinese population. Patients of hereditary transthyretin amyloidosis (ATTR) with Gly83Arg variation predominantly present with blurred vision and most of these cases are reported by ophthalmologists. There is currently no systematic assessment of extraocular features of ATTR with Gly83Arg variation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six patients and two asymptomatic carriers with molecularly confirmed Gly83Arg variation of ATTR from three unrelated families were identified by sequencing the <jats:italic>TTR<\/jats:italic> gene. The clinical, electrophysiological, ultrasonic, and pathological data were collected and analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study included six patients and two carriers with <jats:italic>TTR<\/jats:italic> Gly83Arg mutation, all of whom came from the Han nationality of China. The average age of onset for the six patients was 39 years, and the course of disease ranged from 5 to 19 years. All the patients started with blurred vision, which was diagnosed as vitreous opacity (VO). Most of the patients developed sensory-motor polyneuropathies over years or even more than a decade (4\u201315 years) after VO. However, the heterogeneity of peripheral neuropathies among these patients remained large between families. Autonomic impairment also occurred after VO, with varying degrees of abnormalities seen in the associated autonomic assessments. None of the patients had any symptoms of cardiac impairment, but abnormal results were found in examinations. A combined biopsy of the sural nerve and muscle was also performed. Nerve pathology revealed the moderately reduced myelinated nerve fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is a detailed account of Gly83Arg mutation-related ATTR, focusing on the extraocular presentations of this special variant in Chinese. Clinical features of this variant are early-onset, ocular involvement predominance, neurological, and cardiac involvement along with the disease, and relatively long survival.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2021.821003","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:09:28Z","timestamp":1643864968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhenxian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujun","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchao","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/S1474-4422(11)70246-0","article-title":"Familial amyloid polyneuropathy","volume":"10","author":"Plant\u00e9-Bordeneuve","year":"2011","journal-title":"The Lancet Neurology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1111\/jns.12451","article-title":"The neuropathy in hereditary transthyretin amyloidosis: A narrative review","volume":"26","author":"Tozza","year":"2021","journal-title":"J Peripher Nerv Syst."},{"key":"B3","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3969\/j.issn.1000-4432.2008.01.016","article-title":"Transthyretin Arg-83 mutation in vitreous amyloidosis","volume":"24","author":"Chen","year":"2008","journal-title":"Yan Ke Xue Bao."},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3760\/cma.j.issn.1003-9406.2012.01.004","article-title":"Identification of a TTR gene mutation in a family with hereditary vitreous amyloidosis","volume":"29","author":"Xie","year":"2012","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi."},{"key":"B5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3969\/j.issn.1000-4432.2011.01.011","article-title":"Clinical characteristics and gene analysis of vitreous am yioidosis in a Chinese kindreds","volume":"26","author":"Xu","year":"2013","journal-title":"Chin J Exp Ophthalmol."},{"key":"B6","first-page":"1631","article-title":"Mutation p.G83R in the transthyretin gene is associated with hereditary vitreous amyloidosis in Han Chinese families","volume":"19","author":"Zhang","year":"2013"},{"key":"B7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/eye.2013.217","article-title":"Ophthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation","volume":"28","author":"Liu","year":"2014","journal-title":"Eye (Lond)."},{"key":"B8","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3109\/13506129.2014.892871","article-title":"Chinese familial transthyretin amyloidosis with vitreous involvement is associated with the transthyretin mutation Gly83Arg: a case report and literature review","volume":"21","author":"Yin","year":"2014","journal-title":"Amyloid."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e520","DOI":"10.1111\/aos.13425","article-title":"Familial vitreous amyloidosis resulting from transthyretin variant Gly83Arg","volume":"95","author":"Xie","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"632096","DOI":"10.3389\/fneur.2021.632096","article-title":"Nerve ultrasound comparison between transthyretin familial amyloid polyneuropathy and chronic inflammatory demyelinating polyneuropathy","volume":"12","author":"Du","year":"2021","journal-title":"Front Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3980\/j.issn.2222-3959.2011.03.26","article-title":"Transthyretin Arg-83 mutation in vitreous amyloidosis","volume":"4","author":"Chen","year":"2011","journal-title":"Int J Ophthalmol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3760\/cma.j.issn.1005-1015.2013.01.025","article-title":"Family with familial vitreous amyloidosis with transthyretin Gly83Arg mutation","volume":"29","author":"Xie","year":"2013","journal-title":"Chin J Ocul Fundus Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3760\/cma.j.issn.1005-1015.2016.03.021","article-title":"A family with familial vitreous amyloidosis with transthyretin Gly83Arg mutation","volume":"32","author":"Xie","year":"2016","journal-title":"Chin J Ocul Fundus Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/mus.25257","article-title":"Clinical measures in transthyretin familial amyloid polyneuropathy","volume":"55","author":"Coelho","year":"2017","journal-title":"Muscle Nerve."},{"key":"B15","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/genes12070955","article-title":"Ocular Involvement in Hereditary Amyloidosis","author":"Minnella","year":"2021","journal-title":"Genes (Basel)."},{"key":"B16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ajo.2017.09.001","article-title":"Ocular manifestations of familial transthyretin amyloidosis","volume":"183","author":"Reynolds","year":"2017","journal-title":"Am J Ophthalmol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12883-017-0957-4","article-title":"Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese","volume":"17","author":"Hsu","year":"2017","journal-title":"BMC Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12883-021-02243-3","article-title":"Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort","volume":"21","author":"Pasutharnchat","year":"2021","journal-title":"BMC Neurol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1136\/bjo.81.4.295","article-title":"Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up","volume":"81","author":"Ando","year":"1997","journal-title":"Br J Ophthalmol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1097\/WCO.0000000000000476","article-title":"Familial amyloid polyneuropathy","volume":"30","author":"Adams","year":"2017","journal-title":"Curr Opin Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jchf.2021.05.005","article-title":"Sex-related risk of cardiac involvement in hereditary transthyretin amyloidosis: insights from THAOS JACC","volume":"9","author":"Caponetti","year":"2021","journal-title":"Heart Fail."},{"key":"B22","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.clinph.2017.01.013","article-title":"Peripheral nerve ultrasonography in patients with transthyretin amyloidosis","volume":"128","author":"Podnar","year":"2017","journal-title":"Clin Neurophysiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00415-020-10127-8","article-title":"Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers","volume":"268","author":"Salvalaggio","year":"2021","journal-title":"J Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"fcz032","DOI":"10.1093\/braincomms\/fcz032","article-title":"Clinicopathological correlations of sural nerve biopsies in TTR Val30Met familial amyloid polyneuropathy","volume":"1","author":"Fernandes","year":"2019","journal-title":"Brain Commun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/mus.26723","article-title":"Transthyretin amyloidosis: Putting myopathy on the map","volume":"61","author":"Pinto","year":"2020","journal-title":"Muscle Nerve."},{"key":"B26","doi-asserted-by":"publisher","first-page":"183","DOI":"10.3109\/13506120209114820","article-title":"Amyloid deposition in ocular tissues of patients with familial amyloidotic polyneuropathy (FAP)","volume":"9","author":"Haraoka","year":"2002","journal-title":"Amyloid."},{"key":"B27","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/00007890-199610150-00028","article-title":"De Novo Amyloid Synthesis In Ocular Tissue In Familial Amyloidotic Polyneuropathy After Liver Transplantation","author":"Ando","year":"1996","journal-title":"Transplantation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5841","DOI":"10.1111\/j.1742-4658.2008.06705.x","article-title":"Structural and mutational analyses of protein-protein interactions between transthyretin and retinol-binding protein","volume":"275","author":"Zanotti","year":"2008","journal-title":"FEBS J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1021\/acs.biochem.1c00073","article-title":"Thermodynamic stability and aggregation kinetics of EF helix and EF loop variants of transthyretin","volume":"60","author":"Ferguson","year":"2021","journal-title":"Biochemistry."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1093\/brain\/123.7.1495","article-title":"The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation","volume":"123","author":"Adams","year":"2000","journal-title":"Brain."},{"key":"B31","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/01.TP.0000092307.98347.CB","article-title":"Ten years of international experience with liver transplantation for familial amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy World Transplant Registry","volume":"77","author":"Herlenius","year":"2004","journal-title":"Transplantation."},{"key":"B32","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1001\/archophthalmol.2009.390","article-title":"Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients","volume":"128","author":"Hara","year":"2010","journal-title":"Archives of Ophthalmology."},{"key":"B33","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1212\/WNL.0b013e3182661eb1","article-title":"Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial","volume":"79","author":"Coelho","year":"2012","journal-title":"Neurology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e212","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.04.033","article-title":"Failure of tafamidis to halt progression of Ala36Pro TTR oculomeningovascular amyloidosis","volume":"27","author":"Salvi","year":"2018","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1097\/WCO.0000000000000852","article-title":"Hereditary transthyretin amyloidosis: current treatment","volume":"33","author":"Adams","year":"2020","journal-title":"Curr Opin Neurol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.821003\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:09:35Z","timestamp":1643864975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.821003\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":35,"alternative-id":["10.3389\/fneur.2021.821003"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.821003","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"article-number":"821003"}}